Loss of heterozygosity on chromosomes 9q and 16p in atypical adenomatous hyperplasia concomitant with adenocarcinoma of the lung

Atypical adenomatous; hyperplasia (AAH) has recently been implicated as a p recursor to lung adenocarcinoma. We previously reported loss of heterozygos ity (LOH) in tuberous sclerosis (TSC) gene-associated regions to frequently be observed in lung adenocarcinoma with multiple AAHs. in this study, we a nalyzed LOH in four microsatellite loci on 9q, including the TSC1 gene-asso ciated region, and four loci on 16p, including the TSC2 gene-associated reg ion, in both 18 AAHs and 17 concomitant lung adenocarcinomas from I I patie nts. Seven of 18 (39%) AAHs and 9 of 17 (53%) adenocarcinomas displayed LOH on 9q. Five (28%) AAHs and seven (41%) adenocarcinomas harbored LOH at loc i adjacent to the TSC1 gene. Four of 18 (22%) AAHs and 6 of 17 (35%) adenoc arcinomas displayed LOH on 16p. One (6%) AAH and five (29%) adenocarcinomas harbored LOH at loci adjacent to the TSC2 gene. These findings may indicat e a causal relationship of LOH on 9q and 16p mi a fraction of AAH lesions a nd adenocarcinomas of the lung. Especially, the frequencies of LOH on 9q an d at the TSC1 gene-associated region were high. The TSC1 gene or another ne ighboring tumor suppressor gene on 9q might be involved in an early stage o f the pathogenesis of lung adenocarcinoma.