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Clonality and Evolutionary History of Rhabdomyosarcoma
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نویسنده
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chen l. ,shern j.f. ,wei j.s. ,yohe m.e. ,song y.k. ,hurd l. ,liao h. ,catchpoole d. ,skapek s.x. ,barr f.g. ,hawkins d.s. ,khan j.
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منبع
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plos genetics - 2015 - دوره : 11 - شماره : 3
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چکیده
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To infer the subclonality of rhabdomyosarcoma (rms) and predict the temporal order of genetic events for the tumorigenic process,and to identify novel drivers,we applied a systematic method that takes into account germline and somatic alterations in 44 tumor-normal rms pairs using deep whole-genome sequencing. intriguingly,we find that loss of heterozygosity of 11p15.5 and mutations in ras pathway genes occur early in the evolutionary history of the pax-fusion-negative-rms (pfn-rms) subtype. we discover several early mutations in non-ras mutated samples and predict them to be drivers in pfn-rms including recurrent mutation of pkn1. in contrast,we find that pax-fusion-positive (pfp) subtype tumors have undergone whole-genome duplication in the late stage of cancer evolutionary history and have acquired fewer mutations and subclones than pfn-rms. moreover we predict that the pax3-foxo1 fusion event occurs earlier than the whole genome duplication. our findings provide information critical to the understanding of tumorigenesis of rms.
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آدرس
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genetics branch,oncogenomics section,center for cancer research,national cancer institute,national institutes of health,bethesda,md, United States, genetics branch,oncogenomics section,center for cancer research,national cancer institute,national institutes of health,bethesda,md,united states,pediatric oncology branch,center for cancer research,national institutes of health,bethesda,md, United States, genetics branch,oncogenomics section,center for cancer research,national cancer institute,national institutes of health,bethesda,md, United States, genetics branch,oncogenomics section,center for cancer research,national cancer institute,national institutes of health,bethesda,md,united states,pediatric oncology branch,center for cancer research,national institutes of health,bethesda,md, United States, genetics branch,oncogenomics section,center for cancer research,national cancer institute,national institutes of health,bethesda,md, United States, genetics branch,oncogenomics section,center for cancer research,national cancer institute,national institutes of health,bethesda,md, United States, genetics branch,oncogenomics section,center for cancer research,national cancer institute,national institutes of health,bethesda,md, United States, biospecimens research and tumour bank,the kids research institute,the children’s hospital at westmead,westmead,nsw, Australia, department of pediatrics,division of pediatric hematology/oncology,ut southwestern medical center,dallas,tx, United States, laboratory of pathology,center for cancer research,national cancer institute,national institutes of health,bethesda,md, United States, department of pediatrics,seattle children’s hospital,fred hutchinson cancer research center,seattle,wa, United States, genetics branch,oncogenomics section,center for cancer research,national cancer institute,national institutes of health,bethesda,md,united states,pediatric oncology branch,center for cancer research,national institutes of health,bethesda,md, United States
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Authors
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