Colorectal Adenomatous Polyposis: Heterogeneity of Susceptibility Gene Mutations and Phenotypes in a Cohort of Italian Patients.
Genet Test Mol Biomarkers
; 20(12): 777-785, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27705013
ABSTRACT
AIMS:
Colorectal adenomatous polyposis entailing cancer predisposition is caused by constitutional mutations in different genes. APC is associated with the familial adenomatous polyposis (FAP/AFAP) and MUTYH with the MUTYH-associated polyposis (MAP), while POLE and POLD1 mutations cause the polymerase proofreading-associated polyposis (PPAP).METHODS:
We screened for mutations in patients with multiple adenomas/FAP 121 patients were analyzed for APC and MUTYH mutations, and 36 patients were also evaluated for POLE and POLD1 gene mutations.RESULTS:
We found 20 FAP/AFAP, 15 MAP, and no PPAPsubjects:
pathogenic mutations proved to be heterogeneous, and included 5 APC and 1 MUTYH novel mutations. The mutation detection rate was significantly different between patients with 5-100 polyps and those with >100 polyps (p = 8.154 × 10-7), with APC mutations being associated with an aggressive phenotype (p = 1.279 × 10-9). Mean age at diagnosis was lower in FAP/AFAP compared to MAP (p = 3.055 × 10-4). Mutation-negative probands showed a mean age at diagnosis that was significantly higher than FAP/AFAP (p = 3.46986 × 10-7) and included 45.3% of patients with <30 polyps and 70.9% of patients with no family history.CONCLUSIONS:
This study enlarges the APC and MUTYH mutational spectra, and also evaluated variants of uncertain significance, including the MUTYH p.Gln338His mutation. Moreover this study underscores the phenotypic heterogeneity and genotype-phenotype correlations in a cohort of Italian patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article