Histologic characteristics of non-microsatellite-instable colon adenomas correlate with distinct molecular patterns.
Hum Pathol
; 42(2): 244-53, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-21238786
ABSTRACT
Colon carcinogenesis encompasses the stepwise accumulation of genomic aberrations correlated with the transition of aberrant crypt-adenoma-carcinoma. Recent data have revealed that, in addition to the microsatellite-instable phenotype, the chromosome instability pathway, representing four fifth of the colon carcinoma, could be involved in heterogeneous molecular alterations. Our project was aimed at determining the existence of distinct molecular subtypes in 159 non-microsatellite-instable colon polyps and their correlation with histology and dysplasia, using allelotyping, MGMT promoter gene methylation status, and K-RAS mutation analyses. Allelic imbalance, MGMT methylation, and K-RAS mutations arise in 62%, 39%, and 32% of polyps, respectively. Only 14% of polyps had no alterations. A 2-way hierarchical clustering analysis of the allelic imbalances identified subgroups of polyps according to their allelic imbalance frequency and distribution. Not only tubulovillous adenoma but also high-grade adenomas were correlated with high global allelic imbalance frequency (P = .005 and P = .003), with allelic imbalance at microsatellites targeting chromosomes 1, 6, and 9. In conclusion, the data presented in this study show that a large heterogeneity exists in the molecular patterns of alterations in precancerous colon lesions, favoring different modes of tumor initiation. Therefore, molecular alterations correlated with tubulovillous-type and high-grade dysplasia could represent targets identifying predictive factors of progression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adenoma
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Pólipos do Colo
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Neoplasias do Colo
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Instabilidade de Microssatélites
Tipo de estudo:
Prognostic_studies
Limite:
Aged
/
Female
/
Humans
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Male
Idioma:
En
Revista:
Hum Pathol
Ano de publicação:
2011
Tipo de documento:
Article