Association of genetic defects in primary resected lung adenocarcinoma revealed by targeted allelic imbalance analysis.
Fiche publication
Date publication
octobre 2002
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BEAU-FALLER Michèle, Dr BRONNER Christian, Pr OUDET Pierre
Tous les auteurs :
Cave-Riant F, Cuillerier B, Beau-Faller M, Martinet N, Alla F, Bronner C, Schneider A, Oudet P, Gaub MP
Lien Pubmed
Résumé
Genetic mechanisms underlying origin and progression of lung cancer are still poorly understood, despite the numerous studies which identified many genomic alterations. Using polymorphic microsatellites, allelic imbalances have been frequently found at loci such as 3p, 5q, 8p, 9p and 9q, 11p and 11q, and 17q without either histologic specificity or prognosis value. We report allelotyping results in 54 cases (50 smokers) of primary lung adenocarcinoma (50 men/4 women) resected at one institution. To perform this study, a panel of seven microsatellites were chosen upon their likely involvement in lung cancer or in the cell cycle. A highly sensitive method was designed using fluorescent PCR coupled with quantification on an automated DNA sequencer. We report that at least one allelic imbalance was observed in 87% of adenocarcinoma. Alterations at 17q23 tended to be associated with early stage tumors (I and II) and longer survivals (P = 0.05 and P = 0.06, respectively). Furthermore, concomitant alterations were found at 9p21 and at either 9q34 or 3p24 loci (P = 0.003 and P = 0.004, respectively). The presence of genes coding for TGF-beta receptors I and II at these loci suggests that the TGF-beta/CDK inhibitor P16/P15 signaling pathway might be involved in lung adenocarcinoma development.
Référence
Am J Respir Cell Mol Biol. 2002 Oct;27(4):495-502.