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

Cell Syst 2018 10 26;7(4):422-437.e7. Epub 2018 Sep 26.

Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address:

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cels.2018.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370347PMC
October 2018
446 Reads

Publication Analysis

Top Keywords

tgf-β superfamily
12
tgf-β signaling
8
genes encode
8
tgf-β
6
tgfbr2 avcr2a
4
avcr2a bmpr2
4
receptors tgfbr2
4
bmp5 receptors
4
ligands bmp5
4
expression metastasis-associated
4
bmpr2 smads
4
smads smad2
4
superfamily correlated
4
positively expression
4
alterations tgf-β
4
smad4 alterations
4
tgf-β ligands
4
smad2 smad4
4
correlated positively
4
hotspots genes
4

Similar Publications