2026-04-17T00:45:34Zhttps://recercat.cat/oai/requestoai:recercat.cat:2445/1790622025-12-05T09:34:57Zcom_2072_1057col_2072_478799col_2072_478917
A Pan-cancer analysis reveals high-frequency genetic alterations in mediators of signaling by the tgf-β superfamily
Korkut, Anil
Zaidi, Sobia
Kanchi, Rupa S.
Rao, Shuyun
Gough, Nancy R.
Schultz, Andre
Li, Xubin
Lorenzi, Philip L.
Berger, Ashton C.
Robertson, Gordon
Kwong, Lawrence N.
Datto, Mike
Roszik, Jason
Ling, Shiyun
Ravikumar, Visweswaran
Manyam, Ganiraju
Rao, Arvind
Shelley, Simon
Liu, Yuexin
Ju, Zhenlin
Hansel, Donna
Velasco, Guillermo de
Pennathur, Arjun
Andersen, Jesper B.
O'Rourke, Colm J.
Ohshiro, Kazufumi
Jogunoori, Wilma
Nguyen, Bao-Ngoc
Li, Shulin
Osmanbeyoglu, Hatice U.
Ajani, Jaffer A.
Mani, Sendurai A.
Houseman, Andres
Wiznerowicz, Maciej
Chen, Jian
Gu, Shoujun
Ma, Wencai
Zhang, Jiexin
Tong, Pan
Cancer Genome Atlas Research Network
Mutació (Biologia)
Genètica
Transducció de senyal cel·lular
Factors de creixement
Càncer
Mutation (Biology)
Genetics
Cellular signal transduction
Growth factors
Cancer
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.
2021-07-14T12:17:04Z
2021-07-14T12:17:04Z
2018-10-24
2021-07-14T12:17:04Z
info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
Versió postprint del document publicat a: https://www.cell.com/cell-systems/fulltext/S2405-4712(18)30357-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405471218303570
Cell Systems, 2018, vol. 7, num. 4, p. 422-437.e7
cc-by-nc-nd (c) Elsevier, 2018
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Elsevier
Articles publicats en revistes (Ciències Fisiològiques)