A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily

A Korkut; S Zaidi; RS Kanchi; S Rao; NR Gough; A Schultz; X Li; PL Lorenzi; AC Berger; G Robertson; LN Kwong; M Datto; J Roszik; S Ling; V Ravikumar; G Manyam; A Rao; S Shelley; Y Liu; Z Ju; D Hansel; G de Velasco; A Pennathur; JB Andersen; CJ O'Rourke; K Ohshiro; W Jogunoori; BN Nguyen; S Li; HU Osmanbeyoglu; JA Ajani; SA Mani; A Houseman; M Wiznerowicz; J Chen; S Gu; W Ma; J Zhang; P Tong; AD Cherniack; C Deng; L Resar; SJ Caesar-Johnson; JA Demchok; I Felau; M Kasapi; ML Ferguson; CM Hutter; HJ Sofia; R Tarnuzzer; Z Wang; L Yang; JC Zenklusen; J Zhang; S Chudamani; J Liu; L Lolla; R Naresh; T Pihl; Q Sun; Y Wan; Y Wu; J Cho; T DeFreitas; S Frazer; N Gehlenborg; G Getz; DI Heiman; J Kim; MS Lawrence; P Lin; S Meier; MS Noble; G Saksena; D Voet; H Zhang; B Bernard; N Chambwe; V Dhankani; T Knijnenburg; R Kramer; K Leinonen; Y Liu; M Miller; S Reynolds; I Shmulevich; V Thorsson; W Zhang; R Akbani; BM Broom; AM Hegde; Z Ju; A Korkut; J Li; H Liang; S Ling; W Liu; Y Lu; GB Mills; KS Ng

Journal article

A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily

A Korkut, S Zaidi, RS Kanchi, S Rao, NR Gough, A Schultz, X Li, PL Lorenzi, AC Berger, G Robertson, LN Kwong, M Datto, J Roszik, S Ling, V Ravikumar, G Manyam, A Rao, S Shelley, Y Liu, Z Ju Show all

Cell Systems | CELL PRESS | Published : 2018

DOI: 10.1016/j.cels.2018.08.010

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 an..

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University of Melbourne Researchers

Christopher Hovens Author

Michael Lawrence Author

Alex Boussioutas Author

Niall Corcoran Author

Grants

Awarded by National Institute for Academic Anaesthesia

Funding Acknowledgements

This work was supported by the following grants: NCI: U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, U24 CA210949, U24 CA210950, P30 CA016672, P30 CA016672, and P01 CA130821; DoD/CDMRP: W81XWH-16-1-0237, NIAA: R01AA023146, and VA: I01BX003732.