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

Korkut A, Zaidi S, Kanchi RS, Rao S, Gough NR, Schultz A, Li X, Lorenzi PL, Berger AC, Robertson G, Kwong LN, Datto M, Roszik J, Ling S, Ravikumar V, Manyam G, Rao A, Shelley S, Liu Y, Ju Z, Hansel D, De Velasco G, Pennathur A, Andersen JB, O'Rourke CJ, Ohshiro K, Jogunoori W, Bao-Ngoc Nguyen , Li S, Osmanbeyoglu HU, Ajani JA, Mani SA, Houseman A, Wiznerowicz M, Chen J, Gu S, Ma W, Zhang J, Tong P, Cherniack AD, Deng C, Resar L, Weinstein JN, Mishra L, Akbani R (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 7

Pages Range: 422-437.e7

Journal Issue: 4

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 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.

Involved external institutions

University of Copenhagen Denmark (DK) George Washington University (GWU) United States (USA) (US) University of Texas MD Anderson Cancer Center United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Johns Hopkins University (JHU) United States (USA) (US) Massachusetts Institute of Technology (MIT) United States (USA) (US) Oregon State University (OSU) United States (USA) (US) Poznan University of Medical Sciences / Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu Poland (PL) British Columbia Cancer Agency Canada (CA) Duke University United States (USA) (US) University of Wisconsin - Madison United States (USA) (US) University of California, San Diego United States (USA) (US) Dana–Farber Cancer Institute United States (USA) (US) University of Pittsburgh United States (USA) (US)

How to cite

APA:

Korkut, A., Zaidi, S., Kanchi, R.S., Rao, S., Gough, N.R., Schultz, A.,... Akbani, R. (2018). A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily. Cell Systems, 7(4), 422-437.e7. https://doi.org/10.1016/j.cels.2018.08.010

MLA:

Korkut, Anil, et al. "A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily." Cell Systems 7.4 (2018): 422-437.e7.

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