Journal article
A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily
Cell systems, Vol.7(4), pp.422-437.e7
10/24/2018
DOI: 10.1016/j.cels.2018.08.010
PMCID: PMC6370347
PMID: 30268436
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.
Details
- Title: Subtitle
- A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily
- Creators
- Anil Korkut - The University of Texas MD Anderson Cancer CenterSobia Zaidi - George Washington UniversityRupa S Kanchi - The University of Texas MD Anderson Cancer CenterShuyun Rao - George Washington UniversityNancy R Gough - George Washington UniversityAndre Schultz - The University of Texas MD Anderson Cancer CenterXubin Li - The University of Texas MD Anderson Cancer CenterPhilip L Lorenzi - The University of Texas MD Anderson Cancer CenterAshton C Berger - Massachusetts Institute of TechnologyGordon Robertson - BC Cancer AgencyLawrence N Kwong - The University of Texas MD Anderson Cancer CenterMike Datto - Department of Pathology, Duke School of Medicine Durham, Durham, NC 27710, USAJason Roszik - The University of Texas MD Anderson Cancer CenterShiyun Ling - The University of Texas MD Anderson Cancer CenterVisweswaran Ravikumar - The University of Texas MD Anderson Cancer CenterGaniraju Manyam - The University of Texas MD Anderson Cancer CenterArvind Rao - The University of Texas MD Anderson Cancer CenterSimon Shelley - University of Wisconsin–MadisonYuexin Liu - The University of Texas MD Anderson Cancer CenterZhenlin Ju - The University of Texas MD Anderson Cancer CenterDonna Hansel - University of California, San DiegoGuillermo de Velasco - Harvard UniversityArjun Pennathur - University of PittsburghJesper B Andersen - University of CopenhagenColm J O'Rourke - University of CopenhagenKazufumi Ohshiro - George Washington UniversityWilma Jogunoori - George Washington UniversityBao-Ngoc Nguyen - George Washington UniversityShulin Li - The University of Texas MD Anderson Cancer CenterHatice U Osmanbeyoglu - Memorial Sloan Kettering Cancer CenterJaffer A Ajani - The University of Texas MD Anderson Cancer CenterSendurai A Mani - The University of Texas MD Anderson Cancer CenterAndres Houseman - Oregon State UniversityMaciej Wiznerowicz - Poznan University of Medical SciencesJian Chen - The University of Texas MD Anderson Cancer CenterShoujun Gu - George Washington UniversityWencai Ma - The University of Texas MD Anderson Cancer CenterJiexin Zhang - The University of Texas MD Anderson Cancer CenterPan Tong - The University of Texas MD Anderson Cancer CenterAndrew D Cherniack - Massachusetts Institute of TechnologyChuxia Deng - George Washington UniversityLinda Resar - Johns Hopkins University School of MedicineJohn N Weinstein - The University of Texas MD Anderson Cancer CenterLopa Mishra - George Washington UniversityRehan Akbani - The University of Texas MD Anderson Cancer Center
- Contributors
- Cancer Genome Atlas Research NetworkDeqin Ma - University of Iowa, PathologyMohammed M Milhem - University of Iowa, Internal MedicineAaron D Bossler - University of Iowa, Pathology
- Resource Type
- Journal article
- Publication Details
- Cell systems, Vol.7(4), pp.422-437.e7
- DOI
- 10.1016/j.cels.2018.08.010
- PMID
- 30268436
- PMCID
- PMC6370347
- ISSN
- 2405-4712
- eISSN
- 2405-4720
- Grant note
- U24 CA143843 / NCI NIH HHS R01 CA232741 / NCI NIH HHS I01 BX003732 / BLRD VA R01 CA236591 / NCI NIH HHS U24 CA199461 / NCI NIH HHS U54 HG003079 / NHGRI NIH HHS P30 CA016672 / NCI NIH HHS P01 CA130821 / NCI NIH HHS U24 CA143883 / NCI NIH HHS U24 CA143799 / NCI NIH HHS R01 AA023146 / NIAAA NIH HHS R01 DK102943 / NIDDK NIH HHS P30 CA006973 / NCI NIH HHS R01 CA183793 / NCI NIH HHS R50 CA221675 / NCI NIH HHS U24 CA143867 / NCI NIH HHS U24 CA143858 / NCI NIH HHS U24 CA143882 / NCI NIH HHS U54 HG003067 / NHGRI NIH HHS U24 CA143845 / NCI NIH HHS U24 CA143835 / NCI NIH HHS U54 HG003273 / NHGRI NIH HHS U24 CA143840 / NCI NIH HHS R00 CA207871 / NCI NIH HHS U24 CA144025 / NCI NIH HHS U24 CA143866 / NCI NIH HHS U24 CA210950 / NCI NIH HHS U24 CA210949 / NCI NIH HHS U01 CA230690 / NCI NIH HHS U24 CA143848 / NCI NIH HHS
- Language
- English
- Date published
- 10/24/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
- Record Identifier
- 9984183985202771
Metrics
35 Record Views