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Heiser & Robert Ackland
Multiple mutations drive the development of angiosarcoma, according to a study published in Nature Genetics.
Researchers identified driver mutations in several genes associated with angiogenesis, including PTPRB and PLCG1.
They also found that PLCG1 mutations only occurred alongside mutations in PTPRB.
The investigators believe these findings may explain why angiosarcoma therapies directed at a single target fail to eradicate the disease.
Angiosarcoma is a rare cancer of the blood vessels that can occur spontaneously or develop after radiotherapy or chronic lymphedema.
Previous research indicated that aberrant angiogenesis, including somatic mutations in angiogenesis-signaling genes, drives angiosarcoma. So researchers developed drugs targeting pathways involved in angiogenesis, but these drugs have had little or no success.
“Because this cancer doesn’t respond well to traditional chemotherapy and radiotherapy, it makes sense to develop drugs that target pathways that control blood vessel formation,” said study author Peter Campbell, MD, PhD, of the Wellcome Trust Sanger Institute in the UK.
“We found 2 novel cancer genes that control blood vessel formation which are mutated in this cancer and which could be targeted for treatment of this highly aggressive cancer.”
To identify these genes, Dr Campbell and his colleagues performed whole-genome, whole-exome, and targeted sequencing in samples from patients with angiosarcoma.
Thirty-eight percent of the samples (15/39) carried mutations in genes that control angiogenesis, including PLCG1 and PTPRB.
The researchers identified 14 PTPRB mutations in 10 samples. This included 8 nonsense variants, 3 missense variants, 2 essential splice-site variants, and 1 frameshift insertion.
The investigators also discovered a recurrent mutation in PLCG1, a missense variant encoding p.Arg707Gln, which was present in 3 patient samples. All 3 PLCG1 mutations co-occurred with PTPRB mutations.
The researchers said this discovery may explain why drugs developed for a single target are ineffective in some angiosarcoma patients.
“Not only does our study change the way people view the biology of this tumor, it acts as a guide for future drug trials in angiosarcoma patients,” said study author Adrian Harris, MD, DPhil, of the University of Oxford in the UK.
He noted that researchers can use information from this study to determine if existing drugs could be effective against angiosarcoma. 
Heiser & Robert Ackland
Multiple mutations drive the development of angiosarcoma, according to a study published in Nature Genetics.
Researchers identified driver mutations in several genes associated with angiogenesis, including PTPRB and PLCG1.
They also found that PLCG1 mutations only occurred alongside mutations in PTPRB.
The investigators believe these findings may explain why angiosarcoma therapies directed at a single target fail to eradicate the disease.
Angiosarcoma is a rare cancer of the blood vessels that can occur spontaneously or develop after radiotherapy or chronic lymphedema.
Previous research indicated that aberrant angiogenesis, including somatic mutations in angiogenesis-signaling genes, drives angiosarcoma. So researchers developed drugs targeting pathways involved in angiogenesis, but these drugs have had little or no success.
“Because this cancer doesn’t respond well to traditional chemotherapy and radiotherapy, it makes sense to develop drugs that target pathways that control blood vessel formation,” said study author Peter Campbell, MD, PhD, of the Wellcome Trust Sanger Institute in the UK.
“We found 2 novel cancer genes that control blood vessel formation which are mutated in this cancer and which could be targeted for treatment of this highly aggressive cancer.”
To identify these genes, Dr Campbell and his colleagues performed whole-genome, whole-exome, and targeted sequencing in samples from patients with angiosarcoma.
Thirty-eight percent of the samples (15/39) carried mutations in genes that control angiogenesis, including PLCG1 and PTPRB.
The researchers identified 14 PTPRB mutations in 10 samples. This included 8 nonsense variants, 3 missense variants, 2 essential splice-site variants, and 1 frameshift insertion.
The investigators also discovered a recurrent mutation in PLCG1, a missense variant encoding p.Arg707Gln, which was present in 3 patient samples. All 3 PLCG1 mutations co-occurred with PTPRB mutations.
The researchers said this discovery may explain why drugs developed for a single target are ineffective in some angiosarcoma patients.
“Not only does our study change the way people view the biology of this tumor, it acts as a guide for future drug trials in angiosarcoma patients,” said study author Adrian Harris, MD, DPhil, of the University of Oxford in the UK.
He noted that researchers can use information from this study to determine if existing drugs could be effective against angiosarcoma.
Heiser & Robert Ackland
Multiple mutations drive the development of angiosarcoma, according to a study published in Nature Genetics.
Researchers identified driver mutations in several genes associated with angiogenesis, including PTPRB and PLCG1.
They also found that PLCG1 mutations only occurred alongside mutations in PTPRB.
The investigators believe these findings may explain why angiosarcoma therapies directed at a single target fail to eradicate the disease.
Angiosarcoma is a rare cancer of the blood vessels that can occur spontaneously or develop after radiotherapy or chronic lymphedema.
Previous research indicated that aberrant angiogenesis, including somatic mutations in angiogenesis-signaling genes, drives angiosarcoma. So researchers developed drugs targeting pathways involved in angiogenesis, but these drugs have had little or no success.
“Because this cancer doesn’t respond well to traditional chemotherapy and radiotherapy, it makes sense to develop drugs that target pathways that control blood vessel formation,” said study author Peter Campbell, MD, PhD, of the Wellcome Trust Sanger Institute in the UK.
“We found 2 novel cancer genes that control blood vessel formation which are mutated in this cancer and which could be targeted for treatment of this highly aggressive cancer.”
To identify these genes, Dr Campbell and his colleagues performed whole-genome, whole-exome, and targeted sequencing in samples from patients with angiosarcoma.
Thirty-eight percent of the samples (15/39) carried mutations in genes that control angiogenesis, including PLCG1 and PTPRB.
The researchers identified 14 PTPRB mutations in 10 samples. This included 8 nonsense variants, 3 missense variants, 2 essential splice-site variants, and 1 frameshift insertion.
The investigators also discovered a recurrent mutation in PLCG1, a missense variant encoding p.Arg707Gln, which was present in 3 patient samples. All 3 PLCG1 mutations co-occurred with PTPRB mutations.
The researchers said this discovery may explain why drugs developed for a single target are ineffective in some angiosarcoma patients.
“Not only does our study change the way people view the biology of this tumor, it acts as a guide for future drug trials in angiosarcoma patients,” said study author Adrian Harris, MD, DPhil, of the University of Oxford in the UK.
He noted that researchers can use information from this study to determine if existing drugs could be effective against angiosarcoma.