@article{a807e16f15ed4721bd784a254f167760,
title = "Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types",
abstract = "Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis. Seiler et al. report that 119 splicing factor genes carry putative driver mutations over 33 tumor types in TCGA. The most common mutations appear to be mutually exclusive and are associated with lineage-independent altered splicing. Samples with these mutations show deregulation of cell-autonomous pathways and immune infiltration.",
keywords = "cancer, FUBP1, mutation, RBM10, SF3B1, splicing, SRSF2, U2AF1",
author = "{The Cancer Genome Atlas Research Network} and Michael Seiler and Shouyong Peng and Agrawal, {Anant A.} and James Palacino and Teng Teng and Ping Zhu and Smith, {Peter G.} and Caesar-Johnson, {Samantha J.} and Demchok, {John A.} and Ina Felau and Melpomeni Kasapi and Ferguson, {Martin L.} and Hutter, {Carolyn M.} and Sofia, {Heidi J.} and Roy Tarnuzzer and Zhining Wang and Liming Yang and Zenklusen, {Jean C.} and Zhang, {Jiashan (Julia)} and Sudha Chudamani and Jia Liu and Laxmi Lolla and Rashi Naresh and Todd Pihl and Qiang Sun and Yunhu Wan and Ye Wu and Juok Cho and Timothy DeFreitas and Scott Frazer and Nils Gehlenborg and Gad Getz and Heiman, {David I.} and Jaegil Kim and Lawrence, {Michael S.} and Pei Lin and Sam Meier and Noble, {Michael S.} and Gordon Saksena and Doug Voet and Hailei Zhang and Brady Bernard and Nyasha Chambwe and Varsha Dhankani and Theo Knijnenburg and Roger Kramer and Kalle Leinonen and Yuexin Liu and Michael Miller and Sheila Reynolds and Ilya Shmulevich and Vesteinn Thorsson and Wei Zhang and Rehan Akbani and Broom, {Bradley M.} and Hegde, {Apurva M.} and Zhenlin Ju and Kanchi, {Rupa S.} and Anil Korkut and Jun Li and Han Liang and Shiyun Ling and Wenbin Liu and Yiling Lu and Mills, {Gordon B.} and Ng, {Kwok Shing} and Arvind Rao and Michael Ryan and Jing Wang and Weinstein, {John N.} and Jiexin Zhang and Adam Abeshouse and Joshua Armenia and Debyani Chakravarty and Chatila, {Walid K.} and {de Bruijn}, Ino and Jianjiong Gao and Gross, {Benjamin E.} and Heins, {Zachary J.} and Ritika Kundra and Konnor La and Marc Ladanyi and Augustin Luna and Nissan, {Moriah G.} and Angelica Ochoa and Phillips, {Sarah M.} and Ed Reznik and Francisco Sanchez-Vega and Chris Sander and Nikolaus Schultz and Robert Sheridan and Sumer, {S. Onur} and Yichao Sun and Taylor, {Barry S.} and Jioajiao Wang and Hongxin Zhang and Pavana Anur and Myron Peto and Paul Spellman and Christopher Benz and Stuart, {Joshua M.} and Wong, {Christopher K.} and Christina Yau and Hayes, {D. Neil} and Parker, {Joel S.} and Wilkerson, {Matthew D.} and Adrian Ally and Miruna Balasundaram and Reanne Bowlby and Denise Brooks and Rebecca Carlsen and Eric Chuah and Noreen Dhalla and Robert Holt and Jones, {Steven J.M.} and Katayoon Kasaian and Darlene Lee and Yussanne Ma and Marra, {Marco A.} and Michael Mayo and Moore, {Richard A.} and Mungall, {Andrew J.} and Karen Mungall and Robertson, {A. Gordon} and Sara Sadeghi and Schein, {Jacqueline E.} and Payal Sipahimalani and Angela Tam and Nina Thiessen and Kane Tse and Tina Wong and Berger, {Ashton C.} and Rameen Beroukhim and Cherniack, {Andrew D.} and Carrie Cibulskis and Gabriel, {Stacey B.} and Gao, {Galen F.} and Gavin Ha and Matthew Meyerson and Schumacher, {Steven E.} and Juliann Shih and Kucherlapati, {Melanie H.} and Kucherlapati, {Raju S.} and Stephen Baylin and Leslie Cope and Ludmila Danilova and Bootwalla, {Moiz S.} and Lai, {Phillip H.} and Maglinte, {Dennis T.} and {Van Den Berg}, {David J.} and Weisenberger, {Daniel J.} and Auman, {J. Todd} and Saianand Balu and Tom Bodenheimer and Cheng Fan and Hoadley, {Katherine A.} and Hoyle, {Alan P.} and Jefferys, {Stuart R.} and Jones, {Corbin D.} and Shaowu Meng and Mieczkowski, {Piotr A.} and Mose, {Lisle E.} and Perou, {Amy H.} and Perou, {Charles M.} and Jeffrey Roach and Yan Shi and Simons, {Janae V.} and Tara Skelly and Soloway, {Matthew G.} and Donghui Tan and Umadevi Veluvolu and Huihui Fan and Toshinori Hinoue and Laird, {Peter W.} and Hui Shen and Wanding Zhou and Michelle Bellair and Kyle Chang and Kyle Covington and Creighton, {Chad J.} and Huyen Dinh and Doddapaneni, {Harsha Vardhan} and Donehower, {Lawrence A.} and Jennifer Drummond and Gibbs, {Richard A.} and Robert Glenn and Walker Hale and Yi Han and Jianhong Hu and Viktoriya Korchina and Sandra Lee and Lora Lewis and Wei Li and Xiuping Liu and Margaret Morgan and Donna Morton and Donna Muzny and Jireh Santibanez and Margi Sheth and Eve Shinbrot and Linghua Wang and Min Wang and Wheeler, {David A.} and Liu Xi and Fengmei Zhao and Julian Hess and Appelbaum, {Elizabeth L.} and Matthew Bailey and Cordes, {Matthew G.} and Li Ding and Fronick, {Catrina C.} and Fulton, {Lucinda A.} and Fulton, {Robert S.} and Cyriac Kandoth and Mardis, {Elaine R.} and McLellan, {Michael D.} and Miller, {Christopher A.} and Schmidt, {Heather K.} and Wilson, {Richard K.} and Daniel Crain and Erin Curley and Johanna Gardner and Kevin Lau and David Mallery and Scott Morris and Joseph Paulauskis and Robert Penny and Candace Shelton and Troy Shelton and Mark Sherman and Eric Thompson and Peggy Yena and Jay Bowen and Gastier-Foster, {Julie M.} and Mark Gerken and Leraas, {Kristen M.} and Lichtenberg, {Tara M.} and Ramirez, {Nilsa C.} and Lisa Wise and Erik Zmuda and Niall Corcoran and Tony Costello and Christopher Hovens and Carvalho, {Andre L.} and {de Carvalho}, {Ana C.} and Fregnani, {Jos{\'e} H.} and Adhemar Longatto-Filho and Reis, {Rui M.} and Cristovam Scapulatempo-Neto and Jenette Creaney",
year = "2018",
month = apr,
day = "3",
doi = "10.1016/j.celrep.2018.01.088",
language = "English",
volume = "23",
pages = "282--296.e4",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}
