A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily
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A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily. / Cancer Genome Atlas Research Network.
I: Cell Systems, Bind 7, Nr. 4, 2018, s. 422-437.e1-e7.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily
AU - Korkut, Anil
AU - Zaidi, Sobia
AU - Kanchi, Rupa S
AU - Rao, Shuyun
AU - Gough, Nancy R
AU - Schultz, Andre
AU - Li, Xubin
AU - Lorenzi, Philip L
AU - Berger, Ashton C
AU - Robertson, Gordon
AU - Kwong, Lawrence N
AU - Datto, Mike
AU - Roszik, Jason
AU - Ling, Shiyun
AU - Ravikumar, Visweswaran
AU - Manyam, Ganiraju
AU - Rao, Arvind
AU - Shelley, Simon
AU - Liu, Yuexin
AU - Ju, Zhenlin
AU - Hansel, Donna
AU - de Velasco, Guillermo
AU - Pennathur, Arjun
AU - Andersen, Jesper B
AU - O'Rourke, Colm J
AU - Ohshiro, Kazufumi
AU - Jogunoori, Wilma
AU - Nguyen, Bao-Ngoc
AU - Li, Shulin
AU - Osmanbeyoglu, Hatice U
AU - Ajani, Jaffer A
AU - Mani, Sendurai A
AU - Houseman, Andres
AU - Wiznerowicz, Maciej
AU - Chen, Jian
AU - Gu, Shoujun
AU - Ma, Wencai
AU - Zhang, Jiexin
AU - Tong, Pan
AU - Cherniack, Andrew D
AU - Deng, Chuxia
AU - Resar, Linda
AU - Weinstein, John N
AU - Mishra, Lopa
AU - Akbani, Rehan
AU - Cancer Genome Atlas Research Network
N1 - Copyright © 2018 Elsevier Inc. All rights reserved.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
U2 - 10.1016/j.cels.2018.08.010
DO - 10.1016/j.cels.2018.08.010
M3 - Journal article
C2 - 30268436
VL - 7
SP - 422-437.e1-e7
JO - Cell Systems
JF - Cell Systems
SN - 2405-4712
IS - 4
ER -
ID: 209256866