학술논문
A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily
Document Type
article
Author
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; de Velasco, Guillermo; 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; Cherniack, Andrew D; Deng, Chuxia; Resar, Linda; Network, The Cancer Genome Atlas Research; Caesar-Johnson, Samantha J; Demchok, John A; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L; Hutter, Carolyn M; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I; Kim, Jaegil; Lawrence, Michael S; Lin, Pei; Meier, Sam; Noble, Michael S; Saksena, Gordon; Voet, Doug; Zhang, Hailei; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Knijnenburg, Theo; Kramer, Roger; Leinonen, Kalle; Miller, Michael; Reynolds, Sheila; Shmulevich, Ilya; Thorsson, Vesteinn; Zhang, Wei; Akbani, Rehan; Broom, Bradley M; Hegde, Apurva M; Li, Jun; Liang, Han; Liu, Wenbin; Lu, Yiling
Source
Cell Systems. 7(4)
Subject
Language
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.