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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Frequent mutations of hepatocyte nuclear factor 1 in colorectal cancer with microsatellite instability.

BACKGROUND & AIMS: The TCF1 gene encoding hepatocyte nuclear factor 1 alpha (HNF1), a transcription factor germline mutated in patients with maturity-onset diabetes of the young type 3, was recently found to be frequently inactivated by biallelic alterations in liver adenoma and in rare hepatocellular carcinomas. The impact of HNF1 in colorectal carcinogenesis has not been studied until now. Colorectal cancer is characterized by the existence of different molecular mechanisms known as microsatellite stable or unstable tumors. METHODS: At first, a series of 10 adenomas and 29 colon cancers regardless of microsatellite instability status were screened for TCF1 mutations on the entire coding sequence. RESULTS: Three mutations in microsatellite instability high (MSI-H) tumors were found in the exon 4 polymorphic poly-cytosin (C)(8) or (C)(9) tract and consisted of a cytosin deletion at position 291. To further characterize the prevalence of TCF1 mutations in the subgroup of MSI-H tumors, 52 additional MSI-H samples were screened for exon 4 alterations; 23% of MSI-H tumors (95% confidence interval, 14%-36%) were found to harbor frameshift at the poly-cytosin tract. The (C)(9) allele was significantly more frequently mutated than the (C)(8) allele (22% vs. 8%; P = 0.03), showing a higher instability of the longer repetition. CONCLUSIONS: These results show a role for HNF1 in MSI-H colorectal carcinogenesis.[1]


  1. Frequent mutations of hepatocyte nuclear factor 1 in colorectal cancer with microsatellite instability. Laurent-Puig, P., Plomteux, O., Bluteau, O., Zinzindohoué, F., Jeannot, E., Dahan, K., Kartheuser, A., Chapusot, C., Cugnenc, P.H., Zucman-Rossi, J. Gastroenterology (2003) [Pubmed]
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