source: Clinical cancer research
authors: Guarinos C, Juárez M, Egoavil C, Rodríguez-Soler M, Pérez-Carbonell L, Salas R, Cubiella J, Rodríguez-Moranta F, de-Castro L, Bujanda L, Serradesanferm A, Nicolás-Pérez D, Herráiz M, Fernández-Bañares F, Herreros-de-Tejada A, Aguirre E, Balmaña J, Rincón M L, Pizarro A, Polo-Ortiz F, Castillejo A, Alenda C, Payá A, Soto J L, Jover R summary/abstract:
The present study aimed to determine the prevalence of MUTYH mutations in patients with multiple colonic polyps and to explore the best strategy for diagnosing MUTYH-associated polyposis (MAP) in these patients.
This study included 405 patients with at least 10 colonic polyps each. All cases were genetically tested for the three most frequent MUTYH 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 KRAS-Gly12Cys and BRAF V600E somatic mutations.
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 MUTYH mutation and KRAS Gly12Cys somatic mutation in polyps. BRAF V600E mutation was found in 74% of serrated polyps in MUTYH-negative patients and in none of the polyps of MAP patients.
We observed a low frequency of MUTYH 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 MUTYH gene analysis only in patients heterozygous for recurrent variants.
Hospital General Universitario Alicante, Complexo Hospitalario Universitario de Ourense, Bellvitge University Hospital, Institut de Malaties Digestives i Metabòliques, Hospital Vall d'Hebrón, Complexo Hospitalario de Vigo, Universidad del País Vasco, Hospital Universitario de Canarias, Clínica Universitaria de Navarra, Hospital Mútua de Terrassa, Hospital Puerta de Hierro, Hospital Arnau de Vilanova, Hospital Bidasoa, Hospital Universitario Virgen del Rocío, Hospital Basurto, Hospital General Universitario Elche, Baylor University Medical Center DOI:
10.1158/1078-0432.CCR-13-1490 read more full text source