Melanoma genome sequencing reveals frequent PREX2 mutations
| العنوان: | Melanoma genome sequencing reveals frequent PREX2 mutations |
|---|---|
| المؤلفون: | Scott Mahan, Gad Getz, Antje Sucker, Douglas Voet, Gordon Saksena, Rui Jing, Rhamy Zeid, Michael S. Lawrence, Jennifer A. Wargo, Xiaojia Ren, Scott L. Carter, Stephan N. Wagner, Jordi Barretina, Todd R. Golub, Nikhil Wagle, Trevor J. Pugh, Alexei Protopopov, Stacey Gabriel, Hailei Zhang, Wendy Winckler, Jennifer Baldwin, Kristian Cibulskis, Nicolas Stransky, Papia Ghosh, Yotam Drier, Alex H. Ramos, Elizabeth Nickerson, Levi A. Garraway, Timothy P. Heffernan, Meredith A. Singer, Melissa Parkin, Michael F. Berger, Elena S Ivanova, Matthew Meyerson, Dirk Schadendorf, Lynda Chin, Carrie Sougnez, Eric S. Lander, Yonathan Lissanu Deribe, Robert C. Onofrio, Lauren Ambrogio, Andrey Sivachenko, Daniel Auclair, Ian R. Watson, Kristin G. Ardlie, Eran Hodis, Petar Stojanov, Timothy Fennell |
| المساهمون: | Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Lander, Eric S. |
| المصدر: | eLife PMC Nature |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | driver mutations, Ultraviolet Rays, DNA Mutational Analysis, Medizin, Biology, medicine.disease_cause, Article, Chromosome Breakpoints, medicine, melanoma, PTEN, Guanine Nucleotide Exchange Factors, Humans, Mutation frequency, Human Biology and Medicine, Gene, mouse, Mutation, cancer genomics, Multidisciplinary, Genome, Human, Melanoma, Point mutation, methodology, Oncogenes, Cell Biology, medicine.disease, Molecular biology, Gene Expression Regulation, Neoplastic, Mutagenesis, Registered Report, biology.protein, Sunlight, Reproducibility Project: Cancer Biology, Melanocytes, Human genome, Ectopic expression, DNA Damage |
| الوصف: | Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5–55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)—a PTEN-interacting protein and negative regulator of PTEN in breast cancer—as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma. National Human Genome Research Institute (U.S.) |
| وصف الملف: | application/pdf |
| تدمد: | 1476-4687 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9701c9c4ae74a8f7ad513ae832f599dcTest https://pubmed.ncbi.nlm.nih.gov/25490935Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9701c9c4ae74a8f7ad513ae832f599dc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14764687 |
|---|