| Literature DB >> 30268436 |
Anil Korkut1, Sobia Zaidi2, Rupa S Kanchi1, Shuyun Rao2, Nancy R Gough2, Andre Schultz1, Xubin Li1, Philip L Lorenzi1, Ashton C Berger3, Gordon Robertson4, Lawrence N Kwong5, Mike Datto6, Jason Roszik7, Shiyun Ling1, Visweswaran Ravikumar1, Ganiraju Manyam1, Arvind Rao1, Simon Shelley8, Yuexin Liu1, Zhenlin Ju1, Donna Hansel9, Guillermo de Velasco10, Arjun Pennathur11, Jesper B Andersen12, Colm J O'Rourke12, Kazufumi Ohshiro2, Wilma Jogunoori13, Bao-Ngoc Nguyen2, Shulin Li14, Hatice U Osmanbeyoglu15, Jaffer A Ajani16, Sendurai A Mani5, Andres Houseman17, Maciej Wiznerowicz18, Jian Chen19, Shoujun Gu2, Wencai Ma1, Jiexin Zhang1, Pan Tong1, Andrew D Cherniack3, Chuxia Deng20, Linda Resar21, John N Weinstein22, Lopa Mishra23, Rehan Akbani24.
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.Entities:
Keywords: DNA methylation; Pan-Cancer; TCGA; TGF-β; TGF-β pathway; The Cancer Genome Atlas; cancer; microRNA; mutation hotspot; transcription
Mesh：
Substances：
Year: 2018 PMID： 30268436 PMCID： PMC6370347 DOI： 10.1016/j.cels.2018.08.010
Source DB: PubMed Journal: Cell Syst ISSN： 2405-4712 Impact factor: 10.304