B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P.
Br J Cancer
; 112(2): 403-12, 2015 Jan 20.
Article
em En
| MEDLINE
| ID: mdl-25314065
ABSTRACT
BACKGROUND:
Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor of colon cancer with microsatellite instability (MSI). However, the developmental mechanism of SSA/P remains unknown. We performed genetic analysis and genome-wide DNA methylation analysis in aberrant crypt foci (ACF), SSA/P, and cancer in SSA/P specimens to show a close association between ACF and the SSA/P-cancer sequence. We also evaluated the prevalence and number of ACF in SSA/P patients.METHODS:
ACF in the right-side colon were observed in 36 patients with SSA/Ps alone, 2 with cancers in SSA/P, and 20 normal subjects and biopsied under magnifying endoscopy. B-RAF mutation and MSI were analysed by PCR-restriction fragment length polymorphism (RFLP) and PCR-SSCP, respectively, in 15 ACF, 20 SSA/P, and 2 cancer specimens. DNA methylation array analysis of seven ACF, seven SSA/P, and two cancer in SSA/P specimens was performed using the microarray-based integrated analysis of methylation by isochizomers (MIAMI) method.RESULTS:
B-RAF mutations were frequently detected in ACF, SSA/P, and cancer in SSA/P tissues. The number of methylated genes increased significantly in the order of ACFCONCLUSIONS:
Our results suggest that ACF are precursor lesions of the SSA/P-cancer sequence in patients with SSA/P, where ACF arise by B-RAF mutation and methylation of some of the six identified genes and develop into SSA/Ps through accumulated methylation of these genes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adenoma
/
Neoplasias do Colo
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Proteínas Proto-Oncogênicas B-raf
/
Focos de Criptas Aberrantes
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article