Article Dans Une Revue Human Pathology Année : 2011

Histologic characteristics of non–microsatellite-instable colon adenomas correlate with distinct molecular patterns

Agnès Neuville
  • Fonction : Auteur
Céline Nicolet
  • Fonction : Auteur
Nicolas Meyer
Anne Schneider
  • Fonction : Auteur
Michèle Legrain
  • Fonction : Auteur
Cécile Brigand
  • Fonction : Auteur
Bernard Duclos
  • Fonction : Auteur
Philippe Bachellier
  • Fonction : Auteur
Pierre Oudet
  • Fonction : Auteur
Jean-Pierre Bellocq
  • Fonction : Auteur
Michèle Kedinger
  • Fonction : Auteur
Marie-Pierre Gaub
  • Fonction : Auteur

Résumé

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.
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Dates et versions

hal-03411990 , version 1 (14-11-2023)

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Agnès Neuville, Céline Nicolet, Nicolas Meyer, Anne Schneider, Michèle Legrain, et al.. Histologic characteristics of non–microsatellite-instable colon adenomas correlate with distinct molecular patterns. Human Pathology, 2011, 42 (2), pp.244-253. ⟨10.1016/j.humpath.2010.07.003⟩. ⟨hal-03411990⟩
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