Data from Prevalence and Characteristics of <i>MUTYH</i>-Associated Polyposis in Patients with Multiple Adenomatous and Serrated Polyps

Abstract

<div>Abstract<p><b>Purpose:</b> The present study aimed to determine the prevalence of <i>MUTYH</i> mutations in patients with multiple colonic polyps and to explore the best strategy for diagnosing <i>MUTYH</i>-associated polyposis (MAP) in these patients.</p><p><b>Experimental Design:</b> This study included 405 patients with at least 10 colonic polyps each. All cases were genetically tested for the three most frequent <i>MUTYH</i> mutations. Whole-gene analysis was performed in heterozygous patients and in 216 patients lacking the three most frequent mutations. Polyps from 56 patients were analyzed for the <i>KRAS</i>-Gly12Cys and <i>BRAF</i> V600E somatic mutations.</p><p><b>Results:</b> Twenty-seven (6.7%) patients were diagnosed with MAP, of which 40.8% showed serrated polyps. The sensitivity of studying only the three common variants was 74.1%. Of 216 patients without any monoallelic mutation in common variants, whole-gene analysis revealed biallelic pathogenic mutation in only one. G396D mutation was associated with serrated lesions and older age at diagnosis. There was a strong association between germinal <i>MUTYH</i> mutation and <i>KRAS</i> Gly12Cys somatic mutation in polyps. BRAF V600E mutation was found in 74% of serrated polyps in <i>MUTYH</i>-negative patients and in none of the polyps of MAP patients.</p><p><b>Conclusions:</b> We observed a low frequency of <i>MUTYH</i> mutations among patients with multiple adenomatous and serrated polyps. The MAP phenotype frequently included patients with serrated polyps, especially when G396D mutation was involved. Our results show that somatic molecular markers of polyps can be useful in identifying MAP cases and support the need for the complete <i>MUTYH</i> gene analysis only in patients heterozygous for recurrent variants. <i>Clin Cancer Res; 20(5); 1158–68. ©2014 AACR</i>.</p></div>