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. To date, there are no studies of the TGF-β superfamily of signaling pathways across multiple cancers. This study represents a key starting point for unraveling the role of this complex superfamily in 33 divergent cancer types from over 9,000 patients. |
Recommended Citation GB/T 7714 |
Korkut A.,Zaidi S.,Kanchi R.S.,et al. A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily[J]. Cell Systems,2018,7(4):422-437.e7.
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APA |
Korkut A..,Zaidi S..,Kanchi R.S..,Rao S..,Gough N.R..,Schultz A..,Li X..,Lorenzi P.L..,Berger A.C..,Robertson G..,Kwong L.N..,Datto M..,Roszik J..,Ling S..,Ravikumar V..,Manyam G..,Rao A..,Shelley S..,Liu Y..,...&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.
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