TY - JOUR
T1 - Prevalence and characteristics of mutyh-associated polyposis in patients with multiple adenomatous and serrated polyps
AU - Guarinos, Carla
AU - Juarez, Miriam
AU - Egoavil, Cecilia
AU - Rodriguez-Soler, Maria
AU - Perez-Carbonell, Lucia
AU - Salas, Ramon
AU - Cubiella, Joaquin
AU - Rodriguez-Moranta, Francisco
AU - De-Castro, Luisa
AU - Bujanda, Luis
AU - Serradesanferm, Anna
AU - Nicolas-Pérez, David
AU - Herraiz, Maite
AU - Fernandez-Bañares, Fernando
AU - Herreros-De-Tejada, Alberto
AU - Aguirre, Elena
AU - Balmana, Judith
AU - Rincon, Maria Luisa
AU - Pizarro, Angeles
AU - Polo-Ortiz, Francisco
AU - Castillejo, Adela
AU - Alenda, Cristina
AU - Paya, Artemio
AU - Soto, Jose Luis
AU - Jover, Rodrigo
PY - 2014
Y1 - 2014
N2 - Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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.
AB - Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=84895779653&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-13-1490
DO - 10.1158/1078-0432.CCR-13-1490
M3 - Artículo
C2 - 24470512
AN - SCOPUS:84895779653
SN - 1078-0432
VL - 20
SP - 1158
EP - 1168
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 5
ER -