Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion
Author(s)
Bass, Adam J.; Lawrence, Michael S.; Brace, Lear E.; Ramos, Alex H.; Drier, Yotam; Cibulskis, Kristian; Sougnez, Carrie; Voet, Douglas; Saksena, Gordon; Sivachenko, Andrey; Jing, Rui; Parkin, Melissa; Pugh, Trevor; Verhaak, Roel G.; Stransky, Nicolas; Boutin, Adam T.; Barretina, Jordi; Solit, David B.; Vakiani, Evi; Lander, Eric Steven; ... Show more Show less
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Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 β-catenin–binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events.
Date issued
2011-09Department
Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical ResearchJournal
Nature Genetics
Publisher
Nature Publishing Group
Citation
Bass, Adam J, Michael S Lawrence, Lear E Brace, Alex H Ramos, Yotam Drier, Kristian Cibulskis, Carrie Sougnez, et al. “Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion.” Nature Genetics 43, no. 10 (September 4, 2011): 964-968.
Version: Author's final manuscript
ISSN
1061-4036
1546-1718