Association of genetic defects in primary resected lung adenocarcinoma revealed by targeted allelic imbalance analysis.
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.
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D000328:Adult; D000368:Aged; D000483:Alleles; D002478:Cells, Cultured; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D013058:Mass Spectrometry; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D012907:Smoking; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016212:Transforming Growth Factor beta