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Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion
Open accessAbstract
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.
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Metadata
- Authors
- Bass, A. J., Lawrence, M. S., Brace, L. E., Ramos, A. H., Drier, Y., Cibulskis, K., Sougnez, C., Voet, D., Saksena, G., Sivachenko, A., Jing, R., Parkin, M., Pugh, T., Verhaak, R. G., Stransky, N., Boutin, A. T., Barretina, J., Solit, D. B., Vakiani, E., Shao, W., Mishina, Y., Warmuth, M., Jimenez, J., Chiang, D. Y., Signoretti, S., Kaelin, W. G., Spardy, N., Hahn, W. C., Hoshida, Y., Ogino, S., DePinho, R. A., Chin, L., Garraway, L. A., Fuchs, C. S., Baselga, J., Tabernero, J., Gabriel, S., Lander, E. S., Getz, G., & Meyerson, M.
- Venue
- Nature Genetics
- Published
- 2011-09-04
- Volume
- 43
- Issue
- 10
- Pages
- 964-968
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1524824145
- Cited by
- 309
- References
- 9
- FWCI
- 27.81
- Type
- journal article
- Language
- en
- Open access
- bronze
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