Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion Journal Article
| 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. Jr; 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. |
| Article Title: | Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion |
| Abstract: | 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. © 2011 Nature America, Inc. All rights reserved. |
| Keywords: | primary tumor; gene mutation; gene sequence; gene translocation; major clinical study; gene deletion; exons; cancer recurrence; cancer growth; adenocarcinoma; rna interference; cancer cell culture; cell line, tumor; transcription factors; cell transformation, neoplastic; colorectal carcinoma; colorectal neoplasms; gene rearrangement; sequence alignment; cancer size; gene fusion; oncogene proteins, fusion; chromosome rearrangement; gene dosage; beta catenin; gene knockdown techniques; genome, human; genetic identification; sequence analysis, dna; basic helix-loop-helix leucine zipper transcription factors; qb-snare proteins; transcription factor 7-like 2 protein |
| Journal Title: | Nature Genetics |
| Volume: | 43 |
| Issue: | 10 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2011-09-04 |
| Start Page: | 964 |
| End Page: | 970 |
| Language: | English |
| DOI: | 10.1038/ng.936 |
| PROVIDER: | scopus |
| PUBMED: | 21892161 |
| PMCID: | PMC3802528 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 November 2011" - "CODEN: NGENE" - "Source: Scopus" |
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