We investigated the somatic c.34G>T KRAS transversion as a marker suggestive of MUTYH-associated polyposis (MAP). We compared 86 adenomas and 19 colorectal cancers (CRCs) of 30 MAP patients to 135 adenomas and five CRCs of 47 familial adenomatous polyposis (FAP) patients. The c.34G>T mutation was investigated by DNA sequencing. Secondly, the germline MUTYH gene sequence was analyzed in patients carrying c.34G>T in CRCs diagnosed between 2008 and 2012. The c.34G>T was present in 39.7% of MAP adenomas versus 1.6% of FAP adenomas (P < 0.01). Sensitivity and specificity for detecting MAP were 39.7% and 98%, respectively. Sensitivity increased with the number of adenomas tested (P = 0.039). KRAS exon 2 analysis was performed on 2239 CRC and 2.2% harbored the c.34G>T transversion. Among 28 carriers of the c.34G>T mutation, biallelic MUTYH mutations were detected in seven patients (25%). One patient did not have any polyp or family history and did not fulfill criteria for MUTYH testing. With high specificity, the c.34G>T mutation seems to be a useful and promising test for MAP. For polyposis, it may guide genetic testing toward APC or MUTYH. If routinely performed in CRC patients, it could help to diagnose MUTYH-mutation carriers, even when they don't fulfill genetic testing criteria.
Keywords: KRAS; MUTYH; MUTYH-associated polyposis; adenomatous polyposis; colorectal cancer.
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