Exome sequencing identifies GRIN2A as frequently mutated in melanoma
Xiaomu Wei,Vijay Walia,Jimmy Lin,Jamie K. Teer,Todd D. Prickett,Jared J. Gartner,Sean Davis,Nisc Comparative Sequencing Program,Katherine Stemke-Hale,Michael A. Davies,Jeffrey E. Gershenwald,William A. Robinson,Steven E. Robinson,Steven A. Rosenberg,Yardena Samuels +14 more
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TLDR
This study provides, to the knowledge, the most comprehensive map of genetic alterations in melanoma to date and suggests that the glutamate signaling pathway is involved in this disease.Abstract:
The incidence of melanoma is increasing more than any other cancer, and knowledge of its genetic alterations is limited. To systematically analyze such alterations, we performed whole-exome sequencing of 14 matched normal and metastatic tumor DNAs. Using stringent criteria, we identified 68 genes that appeared to be somatically mutated at elevated frequency, many of which are not known to be genetically altered in tumors. Most importantly, we discovered that TRRAP harbored a recurrent mutation that clustered in one position (p. Ser722Phe) in 6 out of 167 affected individuals (∼4%), as well as a previously unidentified gene, GRIN2A, which was mutated in 33% of melanoma samples. The nature, pattern and functional evaluation of the TRRAP recurrent mutation suggest that TRRAP functions as an oncogene. Our study provides, to our knowledge, the most comprehensive map of genetic alterations in melanoma to date and suggests that the glutamate signaling pathway is involved in this disease.read more
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VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing
Daniel C. Koboldt,Qunyuan Zhang,David E. Larson,Dong Shen,Michael D. McLellan,Ling Lin,Christopher A. Miller,Elaine R. Mardis,Li Ding,Richard K. Wilson +9 more
TL;DR: An analysis tool for the detection of somatic mutations and copy number alterations in exome data from tumor-normal pairs is presented and new light is shed on the landscape of genetic alterations in ovarian cancer.
Journal ArticleDOI
Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma
Alexandra Snyder,Vladimir Makarov,Taha Merghoub,Jianda Yuan,Jesse M. Zaretsky,Alexis Desrichard,Logan A. Walsh,Michael A. Postow,Phillip Wong,Teresa S. Ho,Travis J. Hollmann,Cameron Bruggeman,Kasthuri Kannan,Yanyun Li,Ceyhan Elipenahli,Cailian Liu,Christopher T. Harbison,Lisu Wang,Antoni Ribas,Jedd D. Wolchok,Jedd D. Wolchok,Timothy A. Chan +21 more
TL;DR: In this paper, the authors provide clarification and correction to their article "Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma" (Dec. 4, 2014, issue).
Journal Article
Patterns of Somatic Mutation in Human Cancer Genomes
TL;DR: In this paper, the coding exons of the family of 518 protein kinases were sequenced in 210 cancers of diverse histological types to explore the nature of the information that will be derived from cancer genome sequencing.
Correction: Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma
Timothy A. Chan,Jedd D. Wolchok +1 more
TL;DR: These findings define a genetic basis for benefit from CTLA-4 blockade in melanoma and provide a rationale for examining exomes of patients for whom anti-CTLA- 4 agents are being considered.
Journal ArticleDOI
A landscape of driver mutations in melanoma
Eran Hodis,Ian R. Watson,Ian R. Watson,Gregory V. Kryukov,Gregory V. Kryukov,Gregory V. Kryukov,Stefan T. Arold,Marcin Imielinski,Jean Philippe Theurillat,Elizabeth Nickerson,Daniel Auclair,Liren Li,Liren Li,Chelsea S. Place,Daniel DiCara,Alex H. Ramos,Alex H. Ramos,Michael S. Lawrence,Kristian Cibulskis,Andrey Sivachenko,Douglas Voet,Gordon Saksena,Nicolas Stransky,Robert C. Onofrio,Wendy Winckler,Kristin G. Ardlie,Nikhil Wagle,Nikhil Wagle,Jennifer A. Wargo,Kelly Chong,Donald L. Morton,Katherine Stemke-Hale,Guo Chen,Michael S. Noble,Matthew Meyerson,John E. Ladbury,Michael A. Davies,Jeffrey E. Gershenwald,Stephan N. Wagner,Dave S.B. Hoon,Dirk Schadendorf,Eric S. Lander,Eric S. Lander,Stacey Gabriel,Gad Getz,Levi A. Garraway,Lynda Chin +46 more
TL;DR: The spectrum of driver mutations provided unequivocal genomic evidence for a direct mutagenic role of UV light in melanoma pathogenesis, providing oncogenic insights in BRAF- and NRAS-driven melanoma as well as those without known NRAS/BRAF mutations.
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TL;DR: To determine if PI3Ks are genetically altered in tumorigenesis, they were sequenced in human for the first time and the results allowed us to assess the importance of phosphatidylinositol 3-kinases in neoplasia.
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