Roland Kuiper, Marjolijn Ligtenberg and Nicoline Hoogerbrugge from the Dept. of Human Genetics have been awarded a 572,500 Euro KWF grant to unravel the role of base excision repair gene defects in adenomatous polyposis and colorectal cancer predisposition.
Colorectal cancer (CRC) usually develops from adenomas. Individuals with multiple adenomatous polyps in the colorectum, referred to as adenomatous polyposis, are at increased risk of developing CRC, but for a considerable fraction of patients the underlying genetic defect is still unknown. This KWF project builds upon our very recent discovery that biallelic germline mutations in a base excision repair gene, NTHL1, are associated with adenomatous polyposis and CRC development. Tumors of affected individuals show a very specific mutation spectrum of C>T transitions reflecting the base excision repair defect. Since NTHL1 is, after MUTYH, already the second base excision repair gene associated with adenomatous polyposis, we will unravel the clinical and genetic implications of mutations in all base excision repair genes in adenomatous polyposis. Furthermore, we will establish the somatic mutation signatures in tumors and polyps that will be imperative for recognizing and distinguishing syndromic forms of BER-associated adenomatous polyposis.
Marjolijn Ligtenberg Nicoline Hoogerbrugge
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