Clinicopathological and genotypic characteristics of colorectal cancer patients carrying a germline MUTYH mutation.

Approximately 5-10% of the cases with colorectal cancers have a hereditary cancer syndrome. MUTYH is a DNA base excision repair gene, and its mutation can induce the development of polyposis and colorectal cancer. Additionally, MUTYH repair gene may interact with the DNA mismatch repair system. The aim of this study was to investigate the clinicopathological features of colorectal cancer cases carrying germline MUTYH mutations. Among patients genetically tested using large hereditary cancer panels, data of those carrying germline MUTYH mutations were retrieved from the archive files. Then, the patients who had colorectal cancer were included in the study. Ten male and three female colorectal cancer patients with pathogenic (n=10) and variant of uncertain significance MUTYH mutations (n=3) were included in the study. While seven cases had homozygous MUTYH mutations, six patients carried heterozygous MUTYH mutations. The patients had c.800C>T p.P267L (n=4), c.1353_1355delGGA p.E452del (n=4), c.1087C>T p.Q363 (n=1), c.631G>A p.V211I (n=1), c.180A>G p.R60R (n=1), c.509G>A p.G170E (n=1) and c.650G>A p.R217H (n=1) mutations. The ascending colon was the most common site of involvement. Six cases with homozygous and one case with double heterozygous mutations had polyposis. Cases with homozygous (n=1) and heterozygous (n=1) MUTYH mutations were found to be MSH2-deficient. In both MSH2-deficient cases, the tumors were located in the ascending colon, and the case with a homozygous mutation had >100 polyps. Given that the MUTYH mutation is rarely seen in cases of colorectal cancers, we believe that our findings may contribute to identifying potential clinical and therapeutic implications for individuals with this mutation.