Prevalence and characteristics of MUTYH-associated polyposis in patients with multiple adenomatous and serrated polyps.
OBJECTIVE
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.


METHODS
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.
Authors' Affiliations: Unidad de Investigación, Departments of Pathology, and Gastroenterology, Hospital General Universitario, Alicante; Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Ourense; Department of Gastroenterology, Bellvitge University Hospital; Institut de Malaties Digestives i Metabòliques, CIBERehd, Hospital Clínic; Department of Oncology, Hospital Vall d'Hebrón, Barcelona; Gastroenterology Department, Complexo Hospitalario de Vigo, Vigo; Department of Gastroenterology, Hospital Donostia, CIBERehd, Universidad del País Vasco, San Sebastián; Department of Gastroenterology, Hospital Universitario de Canarias, La Laguna, Tenerife; Department of Gastroenterology, Clínica Universitaria de Navarra, Pamplona; Department of Gastroenterology, Hospital Mútua de Terrassa, Terrassa; Department of Gastroenterology, Hospital Puerta de Hierro, Madrid; Department of Oncology, Hospital Arnau de Vilanova, Lleida; Department of Gastroenterology, Hospital Bidasoa, Irún; Department of Gastroenterology, Hospital Universitario Virgen del Rocío, Sevilla; Department of Gastroenterology, Hospital Basurto, Bilbao; Department of Molecular Genetics, Hospital General Universitario, Elche, Spain; and Gastrointestinal Cancer Research Laboratory, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Carla
C
Guarinos
Miriam
M
Juárez
Cecilia
C
Egoavil
María
M
Rodríguez-Soler
Lucía
L
Pérez-Carbonell
Ramón
R
Salas
Joaquín
J
Cubiella
Francisco
F
Rodríguez-Moranta
Luisa
L
de-Castro
Luis
L
Bujanda
Anna
A
Serradesanferm
David
D
Nicolás-Pérez
Maite
M
Herráiz
Fernando
F
Fernández-Bañares
Alberto
A
Herreros-de-Tejada
Elena
E
Aguirre
Judith
J
Balmaña
María-Luisa
ML
Rincón
Angeles
A
Pizarro
Francisco
F
Polo-Ortiz
Adela
A
Castillejo
Cristina
C
Alenda
Artemio
A
Payá
José-Luis
JL
Soto
Rodrigo
R
Jover
D011125:Adenomatous Polyposis Coli / Q000175:diagnosis* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D003111:Colonic Polyps / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D055815:Young Adult
D048493:Proto-Oncogene Proteins B-raf; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase