Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3.
Marcel Martin,Marcel Martin,Lars Maßhöfer,Petra Temming,Sven Rahmann,Claudia H D Metz,Norbert Bornfeld,Johannes van de Nes,Ludger Klein-Hitpass,Alan G. Hinnebusch,Bernhard Horsthemke,Dietmar R. Lohmann,Michael Zeschnigk +12 more
TLDR
Using exome sequencing, recurrent somatic mutations in EIF1AX and SF3B1 are identified occurring in uveal melanomas with disomy 3, which rarely metastasize and are associated with poor prognosis.Abstract:
Michael Zeschnigk and colleagues identify recurrent somatic mutations of EIF1AX and SF3B1 in uveal melanomas with disomy 3. The EIF1AX mutations specifically alter the N-terminal tail of the protein and were found exclusively in tumors lacking SF3B1 mutations.read more
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Journal ArticleDOI
Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma
A. Gordon Robertson,Juliann Shih,Juliann Shih,Christina Yau,Ewan A. Gibb,Junna Oba,Karen Mungall,Julian M. Hess,Vladislav Uzunangelov,Vonn Walter,Vonn Walter,Ludmila Danilova,Tara M. Lichtenberg,Melanie H. Kucherlapati,Patrick K. Kimes,Ming Tang,Alexander V Penson,Özgün Babur,Rehan Akbani,Christopher A. Bristow,Katherine A. Hoadley,Lisa Iype,Matthew T. Chang,Matthew T. Chang,Mohamed H. Abdel-Rahman,Adrian Ally,J. Todd Auman,Miruna Balasundaram,Saianand Balu,Christopher C. Benz,Rameen Beroukhim,Inanc Birol,Tom Bodenheimer,Jay Bowen,Reanne Bowlby,Denise Brooks,Rebecca Carlsen,Colleen M. Cebulla,Andrew D. Cherniack,Andrew D. Cherniack,Lynda Chin,Juok Cho,Eric Chuah,Sudha Chudamani,Carrie Cibulskis,Kristian Cibulskis,Leslie Cope,Sarah E. Coupland,Timothy Defreitas,John A. Demchok,Laurence Desjardins,Noreen Dhalla,Bita Esmaeli,Ina Felau,Martin L. Ferguson,Scott Frazer,Stacey Gabriel,Julie M. Gastier-Foster,Nils Gehlenborg,Mark Gerken,Jeffrey E. Gershenwald,Gad Getz,Klaus G. Griewank,Elizabeth A. Grimm,D. Neil Hayes,Apurva M. Hegde,David I. Heiman,Carmen Helsel,Shital Hobensack,Robert A. Holt,Alan P. Hoyle,Xin Hu,Carolyn M. Hutter,Martine J. Jager,Stuart R. Jefferys,Corbin D. Jones,Steven J.M. Jones,Cyriac Kandoth,Katayoon Kasaian,Jaegil Kim,Raju Kucherlapati,Eric S. Lander,Michael S. Lawrence,Alexander J. Lazar,Semin Lee,Kristen M. Leraas,Pei Lin,Jia Liu,Wen-Bin Liu,Laxmi Lolla,Yiling Lu,Yussanne Ma,Harshad S. Mahadeshwar,Odette Mariani,Marco A. Marra,Michael Mayo,Sam Meier,Shaowu Meng,Matthew Meyerson,Piotr A. Mieczkowski,Gordon B. Mills,Richard A. Moore,Lisle E. Mose,Andrew J. Mungall,Bradley A. Murray,Rashi Naresh,Michael S. Noble,Angeliki Pantazi,Michael Parfenov,Peter J. Park,Joel S. Parker,Charles M. Perou,Todd Pihl,Robert Pilarski,Alexei Protopopov,Amie Radenbaugh,Karan Rai,Nilsa C. Ramirez,Xiaojia Ren,Sheila Reynolds,Jeffrey Roach,Sergio Roman-Roman,Jason Roszik,Sara Sadeghi,Gordon Saksena,Xavier Sastre,Dirk Schadendorf,Jacqueline E. Schein,Lynn Schoenfield,Steven E. Schumacher,Jonathan G. Seidman,Sahil Seth,Geetika Sethi,Margi Sheth,Yan Shi,Carol L. Shields,Ilya Shmulevich,Janae V. Simons,Arun D. Singh,Payal Sipahimalani,Tara Skelly,Heidi J. Sofia,Matthew G. Soloway,Xingzhi Song,Marc-Henri Stern,Joshua M. Stuart,Qiang Sun,Huandong Sun,Angela Tam,Donghui Tan,Jiabin Tang,Roy Tarnuzzer,Barry S. Taylor,Nina Thiessen,Vesteinn Thorsson,Kane Tse,Umadevi Veluvolu,Roel G.W. Verhaak,Doug Voet,Yunhu Wan,Zhining Wang,John N. Weinstein,Matthew D. Wilkerson,Michelle D. Williams,Lisa Wise,Scott E. Woodman,Tina Wong,Ye Wu,Liming Yang,Lixing Yang,Jean C. Zenklusen,Jiashan Zhang,Hailei Zhang,Erik Zmuda +173 more
TL;DR: Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.
Journal ArticleDOI
RNA splicing factors as oncoproteins and tumour suppressors
TL;DR: The recent genomic characterization of cancers has revealed recurrent somatic point mutations and copy number changes affecting genes encoding RNA splicing factors, which may create novel vulnerabilities in cancer cells that can be therapeutic exploited using compounds that can influence the splicing process.
Journal ArticleDOI
Therapeutic targeting of splicing in cancer
TL;DR: This work presents strategies that exist and that are in development to target altered dependency on the spliceosome, as well as aberrant splicing, in cancer and methods to alter post-translational modifications of splicing-regulating proteins.
Journal ArticleDOI
SF3B1 Mutations Are Associated with Alternative Splicing in Uveal Melanoma
Simon J. Furney,Malin Pedersen,David Gentien,Amaury Dumont,Audrey Rapinat,Laurence Desjardins,Samra Turajlic,Sophie Piperno-Neumann,Pierre de la Grange,Sergio Roman-Roman,Marc-Henri Stern,Richard Marais +11 more
TL;DR: It is shown that SF3B1 is recurrently mutated in uveal melanoma, and the mutations are associated with aberrant alternative splicing, a relatively simple genetic disease characterized by recurrent chromosomal losses and gains and a low mutational burden.
Journal ArticleDOI
Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas
Michael Krauthammer,Yong Kong,Antonella Bacchiocchi,Perry Evans,Natapol Pornputtapong,Cen Wu,James P. McCusker,Shuangge Ma,Elaine Cheng,Robert Straub,Merdan Serin,Marcus Bosenberg,Stephan Ariyan,Deepak Narayan,Mario Sznol,Harriet M. Kluger,Shrikant Mane,Joseph Schlessinger,Richard P. Lifton,Ruth Halaban +19 more
TL;DR: It is concluded that NF1 is a key tumor suppressor lost in melanomas, and that concurrent RASopathy gene mutations may enhance its role in melanomagenesis.
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