ANSWER

For a number of reasons (discussed more fully below), the correct answer is to follow up with the pathologist (choice “c”); the biopsying provider, who is the only person to have seen the lesion, is responsible for resolving any discordance between the report and the clinical presentation/appearance.

Simply accepting the report as fact and notifying the patient of the result (choice “a”) is unacceptable. Removing more tissue from the base of the site (choice “b”) is not likely to provide any useful clinical information. Watching the site for change (choice “d”) ignores the possibility that the original lesion has already spread.

DISCUSSION

Skin tags, also known as fibroepithelioma or acrochorda, are extremely common, benign lesions encountered daily by almost all medical providers. Melanoma in tag form is decidedly unusual, but far from unknown. Around 80% of melanomas are essentially flat (macular), and about 10% are nodular. The rest, from a morphologic standpoint, are all over the map. They can be red, blue, and even white. Contrary to popular misconception, they rarely itch, and you probably wouldn’t want to depend on your dog to alert you to their presence.

My point? Although we conceive of melanomas as looking a certain way (a useful and nec­essary view), the reality is that their morphologic presentations are astonishingly diverse. They include pedunculated tags.

This means that unless we have a very good reason to do otherwise, we should send almost every skin lesion we remove for pathologic examination. Simple, small tags, warts, and the like can be safely discarded. But anything of substance, or anything that appears to be the least bit odd, must be submitted to pathology.

Furthermore, the pathology reports must be carefully read and the results connected to the particular lesion. This case illustrates that necessity nicely. With its black tip, this lesion was more than a little worrisome. When no mention was made of the pigmentary changes, a call to the pathologist was in order.

In this case, the pathologist was more than happy to order new and deeper cuts to be made in the specimen. Within two days, he issued a new report, which showed benign nevoid changes that explained the dark pigment and failed to show any atypia. Then, and only then, were we able to give the results to the patient.

This principle can be extrapolated to results from other types of tests. They are not to be accepted blindly by the ordering provider, who is in the unique position of having seen the patient.

ANSWER

For a number of reasons (discussed more fully below), the correct answer is to follow up with the pathologist (choice “c”); the biopsying provider, who is the only person to have seen the lesion, is responsible for resolving any discordance between the report and the clinical presentation/appearance.

Simply accepting the report as fact and notifying the patient of the result (choice “a”) is unacceptable. Removing more tissue from the base of the site (choice “b”) is not likely to provide any useful clinical information. Watching the site for change (choice “d”) ignores the possibility that the original lesion has already spread.

DISCUSSION

Skin tags, also known as fibroepithelioma or acrochorda, are extremely common, benign lesions encountered daily by almost all medical providers. Melanoma in tag form is decidedly unusual, but far from unknown. Around 80% of melanomas are essentially flat (macular), and about 10% are nodular. The rest, from a morphologic standpoint, are all over the map. They can be red, blue, and even white. Contrary to popular misconception, they rarely itch, and you probably wouldn’t want to depend on your dog to alert you to their presence.

My point? Although we conceive of melanomas as looking a certain way (a useful and nec­essary view), the reality is that their morphologic presentations are astonishingly diverse. They include pedunculated tags.

This means that unless we have a very good reason to do otherwise, we should send almost every skin lesion we remove for pathologic examination. Simple, small tags, warts, and the like can be safely discarded. But anything of substance, or anything that appears to be the least bit odd, must be submitted to pathology.

Furthermore, the pathology reports must be carefully read and the results connected to the particular lesion. This case illustrates that necessity nicely. With its black tip, this lesion was more than a little worrisome. When no mention was made of the pigmentary changes, a call to the pathologist was in order.

In this case, the pathologist was more than happy to order new and deeper cuts to be made in the specimen. Within two days, he issued a new report, which showed benign nevoid changes that explained the dark pigment and failed to show any atypia. Then, and only then, were we able to give the results to the patient.

This principle can be extrapolated to results from other types of tests. They are not to be accepted blindly by the ordering provider, who is in the unique position of having seen the patient.

ANSWER

For a number of reasons (discussed more fully below), the correct answer is to follow up with the pathologist (choice “c”); the biopsying provider, who is the only person to have seen the lesion, is responsible for resolving any discordance between the report and the clinical presentation/appearance.

Simply accepting the report as fact and notifying the patient of the result (choice “a”) is unacceptable. Removing more tissue from the base of the site (choice “b”) is not likely to provide any useful clinical information. Watching the site for change (choice “d”) ignores the possibility that the original lesion has already spread.

DISCUSSION

Skin tags, also known as fibroepithelioma or acrochorda, are extremely common, benign lesions encountered daily by almost all medical providers. Melanoma in tag form is decidedly unusual, but far from unknown. Around 80% of melanomas are essentially flat (macular), and about 10% are nodular. The rest, from a morphologic standpoint, are all over the map. They can be red, blue, and even white. Contrary to popular misconception, they rarely itch, and you probably wouldn’t want to depend on your dog to alert you to their presence.

My point? Although we conceive of melanomas as looking a certain way (a useful and nec­essary view), the reality is that their morphologic presentations are astonishingly diverse. They include pedunculated tags.

This means that unless we have a very good reason to do otherwise, we should send almost every skin lesion we remove for pathologic examination. Simple, small tags, warts, and the like can be safely discarded. But anything of substance, or anything that appears to be the least bit odd, must be submitted to pathology.

Furthermore, the pathology reports must be carefully read and the results connected to the particular lesion. This case illustrates that necessity nicely. With its black tip, this lesion was more than a little worrisome. When no mention was made of the pigmentary changes, a call to the pathologist was in order.

In this case, the pathologist was more than happy to order new and deeper cuts to be made in the specimen. Within two days, he issued a new report, which showed benign nevoid changes that explained the dark pigment and failed to show any atypia. Then, and only then, were we able to give the results to the patient.

This principle can be extrapolated to results from other types of tests. They are not to be accepted blindly by the ordering provider, who is in the unique position of having seen the patient.

When 95 women from Wright-Patterson Air Force Base in Ohio were surveyed about their views of noninvasive prenatal testing (NIPT) versus invasive screening, more than 60% of respondents said they would choose NIPT or no invasive testing if ultrasound screening, a quad screen, or conventional first-trimester screening revealed an abnormality. One-third of respondents said they would likely undergo invasive testing if NIPT results were abnormal, and more than 50% of women in this group reported that the results might influence their decision to continue the pregnancy.

The survey results were presented as a poster at the 2014 American College of Obstetricians and Gynecologists (ACOG) annual clinical meeting in Chicago.¹

All patients attended a group prenatal genetic counseling session led by a single provider in early pregnancy before completing the survey.

The military population surveyed in this study “as a whole is a little bit skewed in race and education,” said Jacqueline Vidosh, MD, a coauthor of the study. That population was predominantly white, with the majority of women having completed at least some college.”

“The nice thing about a military population, however, is that you capture geographical differences, which is a lot harder to do on a small scale,” said Dr. Vidosh.

Andrea Shields, MD, provided the genetic counseling education for the study.

“My class lasted anywhere from 75 minutes to about 90 minutes,” she said, “so it was a considerable time that we took, but it wasn’t specifically devoted to NIPT. That portion took about 10 minutes. But it was introducing them to prenatal diagnosis and screening that took a while, so I think there has to be a large focus on education for any type of prenatal test. Pretest education is extremely important, especially when we’re trying to introduce this technology.”

MORE NEWS and HIGHLIGHTS from ACOG's 2014 ANNUAL CLINICAL MEETING

Ospemifene found to have minimal effects on the endometrium at 52 weeks

Adding infertility assessment and treatment to your practice

Delivery notes after shoulder dystocia often lack critical elements

Why it’s important to open the sexual health dialogue

When 95 women from Wright-Patterson Air Force Base in Ohio were surveyed about their views of noninvasive prenatal testing (NIPT) versus invasive screening, more than 60% of respondents said they would choose NIPT or no invasive testing if ultrasound screening, a quad screen, or conventional first-trimester screening revealed an abnormality. One-third of respondents said they would likely undergo invasive testing if NIPT results were abnormal, and more than 50% of women in this group reported that the results might influence their decision to continue the pregnancy.

The survey results were presented as a poster at the 2014 American College of Obstetricians and Gynecologists (ACOG) annual clinical meeting in Chicago.¹

All patients attended a group prenatal genetic counseling session led by a single provider in early pregnancy before completing the survey.

The military population surveyed in this study “as a whole is a little bit skewed in race and education,” said Jacqueline Vidosh, MD, a coauthor of the study. That population was predominantly white, with the majority of women having completed at least some college.”

“The nice thing about a military population, however, is that you capture geographical differences, which is a lot harder to do on a small scale,” said Dr. Vidosh.

Andrea Shields, MD, provided the genetic counseling education for the study.

“My class lasted anywhere from 75 minutes to about 90 minutes,” she said, “so it was a considerable time that we took, but it wasn’t specifically devoted to NIPT. That portion took about 10 minutes. But it was introducing them to prenatal diagnosis and screening that took a while, so I think there has to be a large focus on education for any type of prenatal test. Pretest education is extremely important, especially when we’re trying to introduce this technology.”

MORE NEWS and HIGHLIGHTS from ACOG's 2014 ANNUAL CLINICAL MEETING

Ospemifene found to have minimal effects on the endometrium at 52 weeks

Adding infertility assessment and treatment to your practice

Delivery notes after shoulder dystocia often lack critical elements

Why it’s important to open the sexual health dialogue

When 95 women from Wright-Patterson Air Force Base in Ohio were surveyed about their views of noninvasive prenatal testing (NIPT) versus invasive screening, more than 60% of respondents said they would choose NIPT or no invasive testing if ultrasound screening, a quad screen, or conventional first-trimester screening revealed an abnormality. One-third of respondents said they would likely undergo invasive testing if NIPT results were abnormal, and more than 50% of women in this group reported that the results might influence their decision to continue the pregnancy.

The survey results were presented as a poster at the 2014 American College of Obstetricians and Gynecologists (ACOG) annual clinical meeting in Chicago.¹

All patients attended a group prenatal genetic counseling session led by a single provider in early pregnancy before completing the survey.

The military population surveyed in this study “as a whole is a little bit skewed in race and education,” said Jacqueline Vidosh, MD, a coauthor of the study. That population was predominantly white, with the majority of women having completed at least some college.”

“The nice thing about a military population, however, is that you capture geographical differences, which is a lot harder to do on a small scale,” said Dr. Vidosh.

Andrea Shields, MD, provided the genetic counseling education for the study.

“My class lasted anywhere from 75 minutes to about 90 minutes,” she said, “so it was a considerable time that we took, but it wasn’t specifically devoted to NIPT. That portion took about 10 minutes. But it was introducing them to prenatal diagnosis and screening that took a while, so I think there has to be a large focus on education for any type of prenatal test. Pretest education is extremely important, especially when we’re trying to introduce this technology.”

MORE NEWS and HIGHLIGHTS from ACOG's 2014 ANNUAL CLINICAL MEETING

Ospemifene found to have minimal effects on the endometrium at 52 weeks

Adding infertility assessment and treatment to your practice

Delivery notes after shoulder dystocia often lack critical elements

Why it’s important to open the sexual health dialogue

Shoulder dystocia is a leading cause of litigation in obstetrics, and the delivery note is an indispensable tool in the defense of a case. When investigators from the University of Southern California analyzed 66 delivery notes to determine how many of 20 intrapartum elements were covered, they found that an average of 11 (58%) were documented. No note included all 20 element.

The study was presented as a poster at the 2014 American College of Obstetricians and Gynecologists annual clinical meeting in Chicago.¹

The 20 elements and their frequency of documentation were:

• date – 96%
• time – 96%
• maneuvers used to achieve delivery – 91%
• order of maneuvers – 89%
• maternal gravidity and parity – 86%
• mode of delivery – 86%
• Apgar scores – 80%
• type of perineal laceration – 80%
• infant birth weight – 77%
• resident provider – 75%
• head-to-body interval – 58%
• cord gases – 53%
• attending provider – 46%
• whether episiotomy was performed – 39%
• application of gentle downward traction – 31%
• movement of the infant’s extremities after delivery – 30%
• which shoulder was anterior – 21%
• whether the patient was informed of the shoulder dystocia – 4%
• adequacy of maternal pelvis – 2%
• lack of fundal pressure – 1%.

Investigators recommended that providers implement use of a standard form to improve recording of critical elements.

MORE NEWS and HIGHLIGHTS from ACOG's 2014 ANNUAL CLINICAL MEETING

Survey: Most average-risk pregnant women preferred NIPT to invasive testing

Adding infertility assessment and treatment to your practice

Ospemifene found to have minimal effects on the endometrium at 52 weeks

Why it’s important to open the sexual health dialogue

Shoulder dystocia is a leading cause of litigation in obstetrics, and the delivery note is an indispensable tool in the defense of a case. When investigators from the University of Southern California analyzed 66 delivery notes to determine how many of 20 intrapartum elements were covered, they found that an average of 11 (58%) were documented. No note included all 20 element.

The study was presented as a poster at the 2014 American College of Obstetricians and Gynecologists annual clinical meeting in Chicago.¹

The 20 elements and their frequency of documentation were:

• date – 96%
• time – 96%
• maneuvers used to achieve delivery – 91%
• order of maneuvers – 89%
• maternal gravidity and parity – 86%
• mode of delivery – 86%
• Apgar scores – 80%
• type of perineal laceration – 80%
• infant birth weight – 77%
• resident provider – 75%
• head-to-body interval – 58%
• cord gases – 53%
• attending provider – 46%
• whether episiotomy was performed – 39%
• application of gentle downward traction – 31%
• movement of the infant’s extremities after delivery – 30%
• which shoulder was anterior – 21%
• whether the patient was informed of the shoulder dystocia – 4%
• adequacy of maternal pelvis – 2%
• lack of fundal pressure – 1%.

Investigators recommended that providers implement use of a standard form to improve recording of critical elements.

MORE NEWS and HIGHLIGHTS from ACOG's 2014 ANNUAL CLINICAL MEETING

Survey: Most average-risk pregnant women preferred NIPT to invasive testing

Adding infertility assessment and treatment to your practice

Ospemifene found to have minimal effects on the endometrium at 52 weeks

Why it’s important to open the sexual health dialogue

Shoulder dystocia is a leading cause of litigation in obstetrics, and the delivery note is an indispensable tool in the defense of a case. When investigators from the University of Southern California analyzed 66 delivery notes to determine how many of 20 intrapartum elements were covered, they found that an average of 11 (58%) were documented. No note included all 20 element.

The study was presented as a poster at the 2014 American College of Obstetricians and Gynecologists annual clinical meeting in Chicago.¹

The 20 elements and their frequency of documentation were:

• date – 96%
• time – 96%
• maneuvers used to achieve delivery – 91%
• order of maneuvers – 89%
• maternal gravidity and parity – 86%
• mode of delivery – 86%
• Apgar scores – 80%
• type of perineal laceration – 80%
• infant birth weight – 77%
• resident provider – 75%
• head-to-body interval – 58%
• cord gases – 53%
• attending provider – 46%
• whether episiotomy was performed – 39%
• application of gentle downward traction – 31%
• movement of the infant’s extremities after delivery – 30%
• which shoulder was anterior – 21%
• whether the patient was informed of the shoulder dystocia – 4%
• adequacy of maternal pelvis – 2%
• lack of fundal pressure – 1%.

Investigators recommended that providers implement use of a standard form to improve recording of critical elements.

MORE NEWS and HIGHLIGHTS from ACOG's 2014 ANNUAL CLINICAL MEETING

Survey: Most average-risk pregnant women preferred NIPT to invasive testing

Adding infertility assessment and treatment to your practice

Ospemifene found to have minimal effects on the endometrium at 52 weeks

Why it’s important to open the sexual health dialogue

Ospemifene was FDA-approved in 2013 to treat moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA) due to menopause. This nonestrogenenic drug has tissue selective agonist/antagonist effects—a selective estrogen-receptor modulator (SERM). Tamoxifen, a first-generation SERM, increases the risk of endometrial cancer. However, the second-generation SERM raloxifene is not associated with this increased risk. In preclinical studies and clinical trials, ospemifene has been shown to exert positive effects on the vaginal epithelium and minimal effects on the endometrium.

Steven R. Goldstein, MD, from New York University School of Medicine, and colleagues set out to determine the endometrial safety of ospemifene in six Phase 2/3 clinical trials of postemenopausal women with up to 52 weeks of exposure to ospemifene 60 mg/day versus placebo.

Endometrial safety of the study drug was assessed in a total of 1,349 women with an intact uterus (851 in the ospemifene group vs 543 in the placebo group).

Results
Endometrial biopsies obtained at 52 weeks revealed a rate of endometrial hyperplasia of 0.3%.

Of 342 biopsied women, “there was a single case of a woman with simple hyperplasia,” says Dr. Goldstein. “She was 52 years old, had become menopausal at age 49 and had been taking hormone therapy for about 2 years before entering the trial. After 4 months of ospemifene, she had an episode of bleeding and was diagnosed with proliferative endometrium. The study drug was stopped with a plan to follow up in 3 months; 89 days later she had another episode of bleeding and was diagnosed with simple hyperplasia. She was treated with a single course of progestogen, the hyperplasia resolved, and then she was noted to have a benign polyp.”

No complex hyperplasias or carcinomas were found.

Ospemifene participants with histologic findings other than inactive, atrophic, or insufficient was 3.5% at 52 weeks, and this finding was similar to baseline endometrial biopsy results for placebo (4.0%).

The incidence of active and disordered type endometrial proliferation was less than 1% of participants treated with ospemifene. The vaginal bleeding incidence was similar in the treatment and placebo groups.

“This data tells me that this drug is clearly acting like its cousin raloxifene in the uterus, with virtually no active proliferation and no true hyperplasia. The FDA guidance for any of these products is less than 1% hyperplasia in 1 year, and there was a single case out of 342 biopsies, says Dr. Goldstein.

MORE NEWS and HIGHLIGHTS from ACOG's 2014 ANNUAL CLINICAL MEETING
Survey: Most average-risk pregnant women preferred NIPT to invasive testing

Adding infertility assessment and treatment to your practice

Delivery notes after shoulder dystocia often lack critical elements

Why it’s important to open the sexual health dialogue

Ospemifene was FDA-approved in 2013 to treat moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA) due to menopause. This nonestrogenenic drug has tissue selective agonist/antagonist effects—a selective estrogen-receptor modulator (SERM). Tamoxifen, a first-generation SERM, increases the risk of endometrial cancer. However, the second-generation SERM raloxifene is not associated with this increased risk. In preclinical studies and clinical trials, ospemifene has been shown to exert positive effects on the vaginal epithelium and minimal effects on the endometrium.

Steven R. Goldstein, MD, from New York University School of Medicine, and colleagues set out to determine the endometrial safety of ospemifene in six Phase 2/3 clinical trials of postemenopausal women with up to 52 weeks of exposure to ospemifene 60 mg/day versus placebo.

Endometrial safety of the study drug was assessed in a total of 1,349 women with an intact uterus (851 in the ospemifene group vs 543 in the placebo group).

Results
Endometrial biopsies obtained at 52 weeks revealed a rate of endometrial hyperplasia of 0.3%.

Of 342 biopsied women, “there was a single case of a woman with simple hyperplasia,” says Dr. Goldstein. “She was 52 years old, had become menopausal at age 49 and had been taking hormone therapy for about 2 years before entering the trial. After 4 months of ospemifene, she had an episode of bleeding and was diagnosed with proliferative endometrium. The study drug was stopped with a plan to follow up in 3 months; 89 days later she had another episode of bleeding and was diagnosed with simple hyperplasia. She was treated with a single course of progestogen, the hyperplasia resolved, and then she was noted to have a benign polyp.”

No complex hyperplasias or carcinomas were found.

Ospemifene participants with histologic findings other than inactive, atrophic, or insufficient was 3.5% at 52 weeks, and this finding was similar to baseline endometrial biopsy results for placebo (4.0%).

The incidence of active and disordered type endometrial proliferation was less than 1% of participants treated with ospemifene. The vaginal bleeding incidence was similar in the treatment and placebo groups.

“This data tells me that this drug is clearly acting like its cousin raloxifene in the uterus, with virtually no active proliferation and no true hyperplasia. The FDA guidance for any of these products is less than 1% hyperplasia in 1 year, and there was a single case out of 342 biopsies, says Dr. Goldstein.

MORE NEWS and HIGHLIGHTS from ACOG's 2014 ANNUAL CLINICAL MEETING
Survey: Most average-risk pregnant women preferred NIPT to invasive testing

Adding infertility assessment and treatment to your practice

Delivery notes after shoulder dystocia often lack critical elements

Why it’s important to open the sexual health dialogue

Ospemifene was FDA-approved in 2013 to treat moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA) due to menopause. This nonestrogenenic drug has tissue selective agonist/antagonist effects—a selective estrogen-receptor modulator (SERM). Tamoxifen, a first-generation SERM, increases the risk of endometrial cancer. However, the second-generation SERM raloxifene is not associated with this increased risk. In preclinical studies and clinical trials, ospemifene has been shown to exert positive effects on the vaginal epithelium and minimal effects on the endometrium.

Steven R. Goldstein, MD, from New York University School of Medicine, and colleagues set out to determine the endometrial safety of ospemifene in six Phase 2/3 clinical trials of postemenopausal women with up to 52 weeks of exposure to ospemifene 60 mg/day versus placebo.

Endometrial safety of the study drug was assessed in a total of 1,349 women with an intact uterus (851 in the ospemifene group vs 543 in the placebo group).

Results
Endometrial biopsies obtained at 52 weeks revealed a rate of endometrial hyperplasia of 0.3%.

Of 342 biopsied women, “there was a single case of a woman with simple hyperplasia,” says Dr. Goldstein. “She was 52 years old, had become menopausal at age 49 and had been taking hormone therapy for about 2 years before entering the trial. After 4 months of ospemifene, she had an episode of bleeding and was diagnosed with proliferative endometrium. The study drug was stopped with a plan to follow up in 3 months; 89 days later she had another episode of bleeding and was diagnosed with simple hyperplasia. She was treated with a single course of progestogen, the hyperplasia resolved, and then she was noted to have a benign polyp.”

No complex hyperplasias or carcinomas were found.

Ospemifene participants with histologic findings other than inactive, atrophic, or insufficient was 3.5% at 52 weeks, and this finding was similar to baseline endometrial biopsy results for placebo (4.0%).

The incidence of active and disordered type endometrial proliferation was less than 1% of participants treated with ospemifene. The vaginal bleeding incidence was similar in the treatment and placebo groups.

“This data tells me that this drug is clearly acting like its cousin raloxifene in the uterus, with virtually no active proliferation and no true hyperplasia. The FDA guidance for any of these products is less than 1% hyperplasia in 1 year, and there was a single case out of 342 biopsies, says Dr. Goldstein.

MORE NEWS and HIGHLIGHTS from ACOG's 2014 ANNUAL CLINICAL MEETING
Survey: Most average-risk pregnant women preferred NIPT to invasive testing

Adding infertility assessment and treatment to your practice

Delivery notes after shoulder dystocia often lack critical elements

Why it’s important to open the sexual health dialogue

Blood sample collection

Credit: Jeremy L. Grisham

An analysis of more than 30,000 individuals has revealed several genetic mutations that appear to play roles in hematologic disorders.

Investigators discovered variants that showed correlations with platelet counts, white blood cell (WBC) counts, hemoglobin concentration, and hematocrit levels.

The group believes these findings could have implications for a range of conditions, including cytopenias, myeloproliferative neoplasms, and stroke.

Guillaume Lettre, PhD, of Université de Montréal and the Montreal Heart Institute in Canada, and his colleagues recounted their discoveries in a letter to Nature Genetics.

The investigators analyzed hemoglobin concentration, hematocrit levels, WBC counts, and platelet counts in 31,340 individuals genotyped on an exome array.

This revealed several missense variants in CXCR2 that were associated with a decreased WBC count. And in a resequencing study, the team identified a CXCR2 frameshift mutation that was associated with congenital neutropenia.

The group also discovered several missense and splice-site variants in genes known to regulate hematopoiesis—TFR2, HBB, TUBB1, SH2B3, and EPO.

A TFR2 mutation (rs139178017) was independently associated with higher hematocrit levels and hemoglobin concentration.

An HBB variant (rs33971440) and an EPO variant (rs62483572), on the other hand, were associated with lower hematocrit levels and hemoglobin concentrations. Further analyses confirmed that having these mutations increased a person’s risk of anemia, with odds ratios of 36.1 and 1.7, respectively.

A TUBB1 missense variant (rs41303899) was associated with decreased platelet count, while 2 missense variants of SH2B3 (rs148636776 and rs72650673) were associated with increased platelet counts.

Lastly, a mutation in JAK2 (rs77375493) was associated with increases in platelets, WBCs, hemoglobin, and hematocrit. And further analyses suggested that individuals with this variant had early stage myeloproliferative neoplasms.

“[T]hese donors also had a higher risk of having a stroke during their lifetime,” said study author Jean-Claude Tardif, MD, of Université de Montréal and the Montreal Heart Institute.

He and his colleagues believe these findings are encouraging, as they provide additional insight into hematologic disorders. But the results also suggest the experimental approach used in this study can be applied to other diseases as well.

Blood sample collection

Credit: Jeremy L. Grisham

An analysis of more than 30,000 individuals has revealed several genetic mutations that appear to play roles in hematologic disorders.

Investigators discovered variants that showed correlations with platelet counts, white blood cell (WBC) counts, hemoglobin concentration, and hematocrit levels.

The group believes these findings could have implications for a range of conditions, including cytopenias, myeloproliferative neoplasms, and stroke.

Guillaume Lettre, PhD, of Université de Montréal and the Montreal Heart Institute in Canada, and his colleagues recounted their discoveries in a letter to Nature Genetics.

The investigators analyzed hemoglobin concentration, hematocrit levels, WBC counts, and platelet counts in 31,340 individuals genotyped on an exome array.

This revealed several missense variants in CXCR2 that were associated with a decreased WBC count. And in a resequencing study, the team identified a CXCR2 frameshift mutation that was associated with congenital neutropenia.

The group also discovered several missense and splice-site variants in genes known to regulate hematopoiesis—TFR2, HBB, TUBB1, SH2B3, and EPO.

A TFR2 mutation (rs139178017) was independently associated with higher hematocrit levels and hemoglobin concentration.

An HBB variant (rs33971440) and an EPO variant (rs62483572), on the other hand, were associated with lower hematocrit levels and hemoglobin concentrations. Further analyses confirmed that having these mutations increased a person’s risk of anemia, with odds ratios of 36.1 and 1.7, respectively.

A TUBB1 missense variant (rs41303899) was associated with decreased platelet count, while 2 missense variants of SH2B3 (rs148636776 and rs72650673) were associated with increased platelet counts.

Lastly, a mutation in JAK2 (rs77375493) was associated with increases in platelets, WBCs, hemoglobin, and hematocrit. And further analyses suggested that individuals with this variant had early stage myeloproliferative neoplasms.

“[T]hese donors also had a higher risk of having a stroke during their lifetime,” said study author Jean-Claude Tardif, MD, of Université de Montréal and the Montreal Heart Institute.

He and his colleagues believe these findings are encouraging, as they provide additional insight into hematologic disorders. But the results also suggest the experimental approach used in this study can be applied to other diseases as well.

Blood sample collection

Credit: Jeremy L. Grisham

An analysis of more than 30,000 individuals has revealed several genetic mutations that appear to play roles in hematologic disorders.

Investigators discovered variants that showed correlations with platelet counts, white blood cell (WBC) counts, hemoglobin concentration, and hematocrit levels.

The group believes these findings could have implications for a range of conditions, including cytopenias, myeloproliferative neoplasms, and stroke.

Guillaume Lettre, PhD, of Université de Montréal and the Montreal Heart Institute in Canada, and his colleagues recounted their discoveries in a letter to Nature Genetics.

The investigators analyzed hemoglobin concentration, hematocrit levels, WBC counts, and platelet counts in 31,340 individuals genotyped on an exome array.

This revealed several missense variants in CXCR2 that were associated with a decreased WBC count. And in a resequencing study, the team identified a CXCR2 frameshift mutation that was associated with congenital neutropenia.

The group also discovered several missense and splice-site variants in genes known to regulate hematopoiesis—TFR2, HBB, TUBB1, SH2B3, and EPO.

A TFR2 mutation (rs139178017) was independently associated with higher hematocrit levels and hemoglobin concentration.

An HBB variant (rs33971440) and an EPO variant (rs62483572), on the other hand, were associated with lower hematocrit levels and hemoglobin concentrations. Further analyses confirmed that having these mutations increased a person’s risk of anemia, with odds ratios of 36.1 and 1.7, respectively.

A TUBB1 missense variant (rs41303899) was associated with decreased platelet count, while 2 missense variants of SH2B3 (rs148636776 and rs72650673) were associated with increased platelet counts.

Lastly, a mutation in JAK2 (rs77375493) was associated with increases in platelets, WBCs, hemoglobin, and hematocrit. And further analyses suggested that individuals with this variant had early stage myeloproliferative neoplasms.

“[T]hese donors also had a higher risk of having a stroke during their lifetime,” said study author Jean-Claude Tardif, MD, of Université de Montréal and the Montreal Heart Institute.

He and his colleagues believe these findings are encouraging, as they provide additional insight into hematologic disorders. But the results also suggest the experimental approach used in this study can be applied to other diseases as well.

Woman sunbathing

Cancer patients with higher levels of vitamin D at diagnosis tend to have better outcomes than patients who are vitamin D-deficient, a meta-analysis suggests.

Researchers found the association between vitamin D and prognosis was most pronounced in patients with breast cancer, colorectal cancer, and lymphomas.

The team observed an association between vitamin D and prognosis in other cancers as well, but the correlations were not significant.

Hui Wang, MD, PhD, of the Chinese Academy of Sciences in Shanghai, China, and colleagues conducted this research and reported their results in the Journal of Clinical Endocrinology & Metabolism.

The team analyzed data from 25 studies including 17,332 cancer patients. In most of the studies, patients had their vitamin D levels tested before they underwent any cancer treatment.

The analysis showed that, overall, a 10 nmol/L increase in vitamin D levels was associated with a 4% increase in survival.

The strongest links between vitamin D levels and survival were seen in breast cancer, colorectal cancer, and lymphomas. There was less evidence of a connection in patients with leukemias, lung cancer, gastric cancer, prostate cancer, melanoma, or Merkel cell carcinoma, but the available data were positive.

There were 2 studies evaluating the association between survival and vitamin D levels in leukemia patients.

Vitamin D insufficiency was associated with poor overall survival in patients with newly diagnosed chronic lymphocytic leukemia, although this was not statistically significant. The hazard ratio (HR) was 0.68 (P=0.07).

For acute myeloid leukemia, patients with vitamin D levels that were considered insufficient (20-31.9 ng/mL) or deficient (<20 ng/mL) had worse overall survival (HR=0.65) and disease-free survival (HR=0.65) than patients with normal vitamin D levels.

There were also 2 studies evaluating the association between survival and vitamin D levels in lymphoma patients. The results showed that patients with the highest vitamin D levels had better overall survival than those with the lowest vitamin D levels (HR=0.48, P<0.001).

Lymphoma patients in the highest quartile of vitamin D levels also had a lower risk of cancer-specific mortality (HR=0.50, P<0.001) and better disease-free survival (HR=0.80, P=0.04).

Similarly, higher vitamin D levels were significantly associated with reduced cancer-specific mortality for patients with colorectal cancer (P=0.005) and improved disease-free survival for patients with breast cancer (P<0.001).

For overall survival, the HR for the highest vs lowest quartile of vitamin D levels was 0.55 for colorectal cancer patients and 0.63 for breast cancer patients.

Based on these results, Dr Wang concluded, “Physicians need to pay close attention to vitamin D levels in people who have been diagnosed with cancer.”

Woman sunbathing

Cancer patients with higher levels of vitamin D at diagnosis tend to have better outcomes than patients who are vitamin D-deficient, a meta-analysis suggests.

Researchers found the association between vitamin D and prognosis was most pronounced in patients with breast cancer, colorectal cancer, and lymphomas.

The team observed an association between vitamin D and prognosis in other cancers as well, but the correlations were not significant.

Hui Wang, MD, PhD, of the Chinese Academy of Sciences in Shanghai, China, and colleagues conducted this research and reported their results in the Journal of Clinical Endocrinology & Metabolism.

The team analyzed data from 25 studies including 17,332 cancer patients. In most of the studies, patients had their vitamin D levels tested before they underwent any cancer treatment.

The analysis showed that, overall, a 10 nmol/L increase in vitamin D levels was associated with a 4% increase in survival.

The strongest links between vitamin D levels and survival were seen in breast cancer, colorectal cancer, and lymphomas. There was less evidence of a connection in patients with leukemias, lung cancer, gastric cancer, prostate cancer, melanoma, or Merkel cell carcinoma, but the available data were positive.

There were 2 studies evaluating the association between survival and vitamin D levels in leukemia patients.

Vitamin D insufficiency was associated with poor overall survival in patients with newly diagnosed chronic lymphocytic leukemia, although this was not statistically significant. The hazard ratio (HR) was 0.68 (P=0.07).

For acute myeloid leukemia, patients with vitamin D levels that were considered insufficient (20-31.9 ng/mL) or deficient (<20 ng/mL) had worse overall survival (HR=0.65) and disease-free survival (HR=0.65) than patients with normal vitamin D levels.

There were also 2 studies evaluating the association between survival and vitamin D levels in lymphoma patients. The results showed that patients with the highest vitamin D levels had better overall survival than those with the lowest vitamin D levels (HR=0.48, P<0.001).

Lymphoma patients in the highest quartile of vitamin D levels also had a lower risk of cancer-specific mortality (HR=0.50, P<0.001) and better disease-free survival (HR=0.80, P=0.04).

Similarly, higher vitamin D levels were significantly associated with reduced cancer-specific mortality for patients with colorectal cancer (P=0.005) and improved disease-free survival for patients with breast cancer (P<0.001).

For overall survival, the HR for the highest vs lowest quartile of vitamin D levels was 0.55 for colorectal cancer patients and 0.63 for breast cancer patients.

Based on these results, Dr Wang concluded, “Physicians need to pay close attention to vitamin D levels in people who have been diagnosed with cancer.”

Woman sunbathing

Cancer patients with higher levels of vitamin D at diagnosis tend to have better outcomes than patients who are vitamin D-deficient, a meta-analysis suggests.

Researchers found the association between vitamin D and prognosis was most pronounced in patients with breast cancer, colorectal cancer, and lymphomas.

The team observed an association between vitamin D and prognosis in other cancers as well, but the correlations were not significant.

Hui Wang, MD, PhD, of the Chinese Academy of Sciences in Shanghai, China, and colleagues conducted this research and reported their results in the Journal of Clinical Endocrinology & Metabolism.

The team analyzed data from 25 studies including 17,332 cancer patients. In most of the studies, patients had their vitamin D levels tested before they underwent any cancer treatment.

The analysis showed that, overall, a 10 nmol/L increase in vitamin D levels was associated with a 4% increase in survival.

The strongest links between vitamin D levels and survival were seen in breast cancer, colorectal cancer, and lymphomas. There was less evidence of a connection in patients with leukemias, lung cancer, gastric cancer, prostate cancer, melanoma, or Merkel cell carcinoma, but the available data were positive.

There were 2 studies evaluating the association between survival and vitamin D levels in leukemia patients.

Vitamin D insufficiency was associated with poor overall survival in patients with newly diagnosed chronic lymphocytic leukemia, although this was not statistically significant. The hazard ratio (HR) was 0.68 (P=0.07).

For acute myeloid leukemia, patients with vitamin D levels that were considered insufficient (20-31.9 ng/mL) or deficient (<20 ng/mL) had worse overall survival (HR=0.65) and disease-free survival (HR=0.65) than patients with normal vitamin D levels.

There were also 2 studies evaluating the association between survival and vitamin D levels in lymphoma patients. The results showed that patients with the highest vitamin D levels had better overall survival than those with the lowest vitamin D levels (HR=0.48, P<0.001).

Lymphoma patients in the highest quartile of vitamin D levels also had a lower risk of cancer-specific mortality (HR=0.50, P<0.001) and better disease-free survival (HR=0.80, P=0.04).

Similarly, higher vitamin D levels were significantly associated with reduced cancer-specific mortality for patients with colorectal cancer (P=0.005) and improved disease-free survival for patients with breast cancer (P<0.001).

For overall survival, the HR for the highest vs lowest quartile of vitamin D levels was 0.55 for colorectal cancer patients and 0.63 for breast cancer patients.

Based on these results, Dr Wang concluded, “Physicians need to pay close attention to vitamin D levels in people who have been diagnosed with cancer.”

Cancer patient receives therapy

Credit: Rhoda Baer

New research indicates that loss of the Y chromosome in the peripheral blood may be associated with decreased survival—both higher mortality from cancer and a shorter life span in general.

Study investigators say their findings may explain why cancer incidence and mortality are both higher in men than in women, and why men have shorter average life spans than women.

Lars Forsberg, PhD, of Uppsala University in Sweden, and his colleagues recounted their findings in Nature Genetics.

The team analyzed blood samples from 1153 elderly men and found the most common genetic alteration was a loss of the Y chromosome in a proportion of leukocytes.

Further analyses revealed that loss of chromosome Y was associated with an increase in cancer diagnosis, cancer mortality, and all-cause mortality.

Specifically, the hazard ratio (HR) was 1.91 (P=0.010) for all-cause mortality and 3.29 (P=0.003) for cancer mortality. The HRs were 3.62 (P=0.003) for non-hematologic cancer mortality and 2.19 (P=0.450) for hematologic cancer mortality.

The HR for a diagnosis of any cancer was 2.47 (P=0.014). And the HR for diagnosis of a non-hematologic malignancy was 2.68 (P=0.008).

The investigators said these results suggest that chromosome Y is important in processes beyond sex determination.

“You have probably heard before that the Y chromosome is small, insignificant, and contains very little genetic information; this is not true,” said study author Jan Dumanski, PhD, of Uppsala University.

“Our results indicate that the Y chromosome has a role in tumor suppression, and they might explain why men get cancer more often than women. We believe that analyses of the Y chromosome could, in the future, become a useful general marker to predict the risk for men to develop cancer.”

Cancer patient receives therapy

Credit: Rhoda Baer

New research indicates that loss of the Y chromosome in the peripheral blood may be associated with decreased survival—both higher mortality from cancer and a shorter life span in general.

Study investigators say their findings may explain why cancer incidence and mortality are both higher in men than in women, and why men have shorter average life spans than women.

Lars Forsberg, PhD, of Uppsala University in Sweden, and his colleagues recounted their findings in Nature Genetics.

The team analyzed blood samples from 1153 elderly men and found the most common genetic alteration was a loss of the Y chromosome in a proportion of leukocytes.

Further analyses revealed that loss of chromosome Y was associated with an increase in cancer diagnosis, cancer mortality, and all-cause mortality.

Specifically, the hazard ratio (HR) was 1.91 (P=0.010) for all-cause mortality and 3.29 (P=0.003) for cancer mortality. The HRs were 3.62 (P=0.003) for non-hematologic cancer mortality and 2.19 (P=0.450) for hematologic cancer mortality.

The HR for a diagnosis of any cancer was 2.47 (P=0.014). And the HR for diagnosis of a non-hematologic malignancy was 2.68 (P=0.008).

The investigators said these results suggest that chromosome Y is important in processes beyond sex determination.

“You have probably heard before that the Y chromosome is small, insignificant, and contains very little genetic information; this is not true,” said study author Jan Dumanski, PhD, of Uppsala University.

“Our results indicate that the Y chromosome has a role in tumor suppression, and they might explain why men get cancer more often than women. We believe that analyses of the Y chromosome could, in the future, become a useful general marker to predict the risk for men to develop cancer.”

Cancer patient receives therapy

Credit: Rhoda Baer

New research indicates that loss of the Y chromosome in the peripheral blood may be associated with decreased survival—both higher mortality from cancer and a shorter life span in general.

Study investigators say their findings may explain why cancer incidence and mortality are both higher in men than in women, and why men have shorter average life spans than women.

Lars Forsberg, PhD, of Uppsala University in Sweden, and his colleagues recounted their findings in Nature Genetics.

The team analyzed blood samples from 1153 elderly men and found the most common genetic alteration was a loss of the Y chromosome in a proportion of leukocytes.

Further analyses revealed that loss of chromosome Y was associated with an increase in cancer diagnosis, cancer mortality, and all-cause mortality.

Specifically, the hazard ratio (HR) was 1.91 (P=0.010) for all-cause mortality and 3.29 (P=0.003) for cancer mortality. The HRs were 3.62 (P=0.003) for non-hematologic cancer mortality and 2.19 (P=0.450) for hematologic cancer mortality.

The HR for a diagnosis of any cancer was 2.47 (P=0.014). And the HR for diagnosis of a non-hematologic malignancy was 2.68 (P=0.008).

The investigators said these results suggest that chromosome Y is important in processes beyond sex determination.

“You have probably heard before that the Y chromosome is small, insignificant, and contains very little genetic information; this is not true,” said study author Jan Dumanski, PhD, of Uppsala University.

“Our results indicate that the Y chromosome has a role in tumor suppression, and they might explain why men get cancer more often than women. We believe that analyses of the Y chromosome could, in the future, become a useful general marker to predict the risk for men to develop cancer.”

Child with ALL

Credit: Bill Branson

The US Food and Drug Administration (FDA) has approved an oral suspension of mercaptopurine (Purixan), a drug used in combination therapy to treat patients with acute lymphoblastic leukemia (ALL).

Mercaptopurine will now be available as a 20 mg/mL oral suspension.

The drug was originally approved as a 50 mg tablet in 1953 and, since that time, has only been commercially available in this form.

Unfortunately, a 50 mg tablet is not ideal because of the age and weight range of children with ALL.

The tablet does not allow for easy body-surface-area dosing and dose adjustments. In addition, tablets can be difficult to administer to children younger than 6 years of age.

To overcome these issues, physicians have used ad hoc local formulations of mercaptopurine compounded in pharmacies or recommended splitting tablets to provide children with the desired dose.

According to the FDA, offering mercaptopurine as a suspension will allow for more accurate delivery of the desired dose to children with a wide range of weights. And a commercially produced suspension is likely to provide a more consistent dose of 6-mercaptopurine than ad hoc compounded formulations.

The FDA’s approval of mercaptopurine as a 20 mg/mL oral suspension is based on results of a clinical pharmacology study. The goal of the study was to assess the bioequivalence of mercaptopurine from a  tablet with that of the mercaptopurine oral suspension in a healthy adult population.

The starting dose of mercaptopurine in multi-agent combination chemotherapy maintenance regimens is 1.5 mg/kg to 2.5 mg/kg (50 mg/m² to 75 mg/m²) as a single, daily dose.

After initiating mercaptopurine, continuation of appropriate dosing requires periodic monitoring of absolute neutrophil counts and platelet counts to assure sufficient drug exposure and to adjust for excessive hematologic toxicity.

Mercaptopurine is distributed by Rare Disease Therapeutics, Inc., in Nashville, Tennessee. For more details on the drug, see the prescribing information.

Child with ALL

Credit: Bill Branson

The US Food and Drug Administration (FDA) has approved an oral suspension of mercaptopurine (Purixan), a drug used in combination therapy to treat patients with acute lymphoblastic leukemia (ALL).

Mercaptopurine will now be available as a 20 mg/mL oral suspension.

The drug was originally approved as a 50 mg tablet in 1953 and, since that time, has only been commercially available in this form.

Unfortunately, a 50 mg tablet is not ideal because of the age and weight range of children with ALL.

The tablet does not allow for easy body-surface-area dosing and dose adjustments. In addition, tablets can be difficult to administer to children younger than 6 years of age.

To overcome these issues, physicians have used ad hoc local formulations of mercaptopurine compounded in pharmacies or recommended splitting tablets to provide children with the desired dose.

According to the FDA, offering mercaptopurine as a suspension will allow for more accurate delivery of the desired dose to children with a wide range of weights. And a commercially produced suspension is likely to provide a more consistent dose of 6-mercaptopurine than ad hoc compounded formulations.

The FDA’s approval of mercaptopurine as a 20 mg/mL oral suspension is based on results of a clinical pharmacology study. The goal of the study was to assess the bioequivalence of mercaptopurine from a  tablet with that of the mercaptopurine oral suspension in a healthy adult population.

The starting dose of mercaptopurine in multi-agent combination chemotherapy maintenance regimens is 1.5 mg/kg to 2.5 mg/kg (50 mg/m² to 75 mg/m²) as a single, daily dose.

After initiating mercaptopurine, continuation of appropriate dosing requires periodic monitoring of absolute neutrophil counts and platelet counts to assure sufficient drug exposure and to adjust for excessive hematologic toxicity.

Mercaptopurine is distributed by Rare Disease Therapeutics, Inc., in Nashville, Tennessee. For more details on the drug, see the prescribing information.

Child with ALL

Credit: Bill Branson

The US Food and Drug Administration (FDA) has approved an oral suspension of mercaptopurine (Purixan), a drug used in combination therapy to treat patients with acute lymphoblastic leukemia (ALL).

Mercaptopurine will now be available as a 20 mg/mL oral suspension.

The drug was originally approved as a 50 mg tablet in 1953 and, since that time, has only been commercially available in this form.

Unfortunately, a 50 mg tablet is not ideal because of the age and weight range of children with ALL.

The tablet does not allow for easy body-surface-area dosing and dose adjustments. In addition, tablets can be difficult to administer to children younger than 6 years of age.

To overcome these issues, physicians have used ad hoc local formulations of mercaptopurine compounded in pharmacies or recommended splitting tablets to provide children with the desired dose.

According to the FDA, offering mercaptopurine as a suspension will allow for more accurate delivery of the desired dose to children with a wide range of weights. And a commercially produced suspension is likely to provide a more consistent dose of 6-mercaptopurine than ad hoc compounded formulations.

The FDA’s approval of mercaptopurine as a 20 mg/mL oral suspension is based on results of a clinical pharmacology study. The goal of the study was to assess the bioequivalence of mercaptopurine from a  tablet with that of the mercaptopurine oral suspension in a healthy adult population.

The starting dose of mercaptopurine in multi-agent combination chemotherapy maintenance regimens is 1.5 mg/kg to 2.5 mg/kg (50 mg/m² to 75 mg/m²) as a single, daily dose.

After initiating mercaptopurine, continuation of appropriate dosing requires periodic monitoring of absolute neutrophil counts and platelet counts to assure sufficient drug exposure and to adjust for excessive hematologic toxicity.

Mercaptopurine is distributed by Rare Disease Therapeutics, Inc., in Nashville, Tennessee. For more details on the drug, see the prescribing information.

Induced pluripotent stem cells

Salk Institute

Retrotransposons—viral elements incorporated into the human genome—may play a key role in maintaining stem cell pluripotency, a new study suggests.

Previous research indicated that an important fraction of mammalian transcriptomes consists of transcripts derived from retrotransposon elements, but the biological function of these transcripts was unknown.

Now, experiments in induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) have provided some insight into the transcripts’ function.

Piero Carninci, PhD, of RIKEN Center for Life Science Technologies in Yokohama, Japan, and his colleagues described these findings in Nature Genetics.

The researchers found that thousands of transcripts in stem cells that have not yet been annotated are transcribed from retrotransposons, presumably to elicit nuclear functions. These transcripts were expressed in iPSCs and ESCs but not in differentiated cells.

Furthermore, several of the transcripts were shown to be involved in the maintenance of pluripotency. Degrading them using RNA interference caused iPSCs to lose their pluripotency and differentiate.

The researchers said these transcripts appear to have been recruited, both in the human and mouse genome, where they are used to maintain the pluripotency of stem cells. But more research is needed to determine exactly how and why this occurs.

“Our work has just begun to unravel the scale of unexpected functions carried out by retrotransposons and their derived transcripts in stem cell biology,” Dr Carninci said.

“We were extremely surprised to learn from our data that what was once considered genetic junk—namely, ancient retroviruses that were thought to just parasite the genome—are, in reality, symbiotic elements that work closely with other genes to maintain [iPSCs and ESCs] in their undifferentiated state.”

Induced pluripotent stem cells

Salk Institute

Retrotransposons—viral elements incorporated into the human genome—may play a key role in maintaining stem cell pluripotency, a new study suggests.

Previous research indicated that an important fraction of mammalian transcriptomes consists of transcripts derived from retrotransposon elements, but the biological function of these transcripts was unknown.

Now, experiments in induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) have provided some insight into the transcripts’ function.

Piero Carninci, PhD, of RIKEN Center for Life Science Technologies in Yokohama, Japan, and his colleagues described these findings in Nature Genetics.

The researchers found that thousands of transcripts in stem cells that have not yet been annotated are transcribed from retrotransposons, presumably to elicit nuclear functions. These transcripts were expressed in iPSCs and ESCs but not in differentiated cells.

Furthermore, several of the transcripts were shown to be involved in the maintenance of pluripotency. Degrading them using RNA interference caused iPSCs to lose their pluripotency and differentiate.

The researchers said these transcripts appear to have been recruited, both in the human and mouse genome, where they are used to maintain the pluripotency of stem cells. But more research is needed to determine exactly how and why this occurs.

“Our work has just begun to unravel the scale of unexpected functions carried out by retrotransposons and their derived transcripts in stem cell biology,” Dr Carninci said.

“We were extremely surprised to learn from our data that what was once considered genetic junk—namely, ancient retroviruses that were thought to just parasite the genome—are, in reality, symbiotic elements that work closely with other genes to maintain [iPSCs and ESCs] in their undifferentiated state.”

Induced pluripotent stem cells

Salk Institute

Retrotransposons—viral elements incorporated into the human genome—may play a key role in maintaining stem cell pluripotency, a new study suggests.

Previous research indicated that an important fraction of mammalian transcriptomes consists of transcripts derived from retrotransposon elements, but the biological function of these transcripts was unknown.

Now, experiments in induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) have provided some insight into the transcripts’ function.

Piero Carninci, PhD, of RIKEN Center for Life Science Technologies in Yokohama, Japan, and his colleagues described these findings in Nature Genetics.

The researchers found that thousands of transcripts in stem cells that have not yet been annotated are transcribed from retrotransposons, presumably to elicit nuclear functions. These transcripts were expressed in iPSCs and ESCs but not in differentiated cells.

Furthermore, several of the transcripts were shown to be involved in the maintenance of pluripotency. Degrading them using RNA interference caused iPSCs to lose their pluripotency and differentiate.

The researchers said these transcripts appear to have been recruited, both in the human and mouse genome, where they are used to maintain the pluripotency of stem cells. But more research is needed to determine exactly how and why this occurs.

“Our work has just begun to unravel the scale of unexpected functions carried out by retrotransposons and their derived transcripts in stem cell biology,” Dr Carninci said.

“We were extremely surprised to learn from our data that what was once considered genetic junk—namely, ancient retroviruses that were thought to just parasite the genome—are, in reality, symbiotic elements that work closely with other genes to maintain [iPSCs and ESCs] in their undifferentiated state.”