Gastroenterology

Gastroenterology

Volume 145, Issue 3, September 2013, Pages 540-543.e22
Gastroenterology

Original Research
Brief Report
Identification of Candidate Oncogenes in Human Colorectal Cancers With Microsatellite Instability

https://doi.org/10.1053/j.gastro.2013.05.015Get rights and content

Microsatellite instability can be found in approximately 15% of all colorectal cancers. To detect new oncogenes we sequenced the exomes of 25 colorectal tumors and respective healthy colon tissue. Potential mutation hot spots were confirmed in 15 genes; ADAR, DCAF12L2, GLT1D1, ITGA7, MAP1B, MRGPRX4, PSRC1, RANBP2, RPS6KL1, SNCAIP, TCEAL6, TUBB6, WBP5, VEGFB, and ZBTB2; these were validated in 86 tumors with microsatellite instability. ZBTB2, RANBP2, and PSRC1 also were found to contain hot spot mutations in the validation set. The form of ZBTB2 associated with colorectal cancer increased cell proliferation. The mutation hot spots might be used to develop personalized tumor profiling and therapy.

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Acknowledgments

The authors thank Sini Nieminen, Sirpa Soisalo, Mairi Kuris, Inga-Lill Svedberg, Sini Miettinen, Iina Vuoristo, Sini Karjalainen, Kati Kämpjärvi, Yilong Li, Miika Mehine, Tatiana Cajuso, and Felicia Wang for technical assistance. The authors also thank Dr Ian Tomlinson for providing some of the colorectal cancer cell lines used in this study.

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Author names in bold designate shared co-first authorship.

Conflicts of interest The authors disclose no conflicts.

Funding Supported by grants from the Academy of Finland (Finnish Center of Excellence Program 2006-2011 and 2012-2017), The Finnish Cancer Society, The Sigrid Juselius Foundation, The Finnish Medical Society Duodecim, and The Cancer Foundation of Irja Karvonen. The Maud Kuistila Foundation, Finska Läkarsällskapet, The Biomedicum Helsinki Foundation, and Jalmari and Rauha Ahokas Foundation.

Authors share co-first authorship.

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