@article{da644b17854e4b42811870e32dbd2675,
title = "A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily",
abstract = "We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-β signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) in 39% of samples, with highest frequencies in gastrointestinal cancers. We identified mutation hotspots in genes that encode TGF-β ligands (BMP5), receptors (TGFBR2, AVCR2A, and BMPR2), and Smads (SMAD2 and SMAD4). Alterations in the TGF-β superfamily correlated positively with expression of metastasis-associated genes and with decreased survival. Correlation analyses showed the contributions of mutation, amplification, deletion, DNA methylation, and miRNA expression to transcriptional activity of TGF-β signaling in each cancer type. This study provides a broad molecular perspective relevant for future functional and therapeutic studies of the diverse cancer pathways mediated by the TGF-β superfamily. To date, there are no studies of the TGF-β superfamily of signaling pathways across multiple cancers. This study represents a key starting point for unraveling the role of this complex superfamily in 33 divergent cancer types from over 9,000 patients.",
keywords = "cancer, DNA methylation, microRNA, mutation hotspot, Pan-Cancer, TCGA, TGF-β, TGF-β pathway, The Cancer Genome Atlas, transcription",
author = "{The Cancer Genome Atlas Research Network} and Anil Korkut and Sobia Zaidi and Kanchi, {Rupa S.} and Shuyun Rao and Gough, {Nancy R.} and Andre Schultz and Xubin Li and Lorenzi, {Philip L.} and Berger, {Ashton C.} and Gordon Robertson and Kwong, {Lawrence N.} and Mike Datto and Jason Roszik and Shiyun Ling and Visweswaran Ravikumar and Ganiraju Manyam and Arvind Rao and Simon Shelley and Yuexin Liu and Zhenlin Ju and Donna Hansel and {de Velasco}, Guillermo and Arjun Pennathur and Andersen, {Jesper B.} and O'Rourke, {Colm J.} and Kazufumi Ohshiro and Wilma Jogunoori and Nguyen, {Bao Ngoc} and Shulin Li and Osmanbeyoglu, {Hatice U.} and Ajani, {Jaffer A.} and Mani, {Sendurai A.} and Andres Houseman and Maciej Wiznerowicz and Jian Chen and Shoujun Gu and Wencai Ma and Jiexin Zhang and Pan Tong and Cherniack, {Andrew D.} and Chuxia Deng and Linda Resar 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 Jenette Creaney",
year = "2018",
month = oct,
day = "24",
doi = "10.1016/j.cels.2018.08.010",
language = "English",
volume = "7",
pages = "422--437.e7",
journal = "Cell Systems",
issn = "2405-4712",
publisher = "Cell Press",
number = "4",
}
