title: Loss of heterozygosity on chromosomes 9q and 16p in atypical adenomatous hyperplasia concomitant with adenocarcinoma of the lung.
abstract: Atypical adenomatous hyperplasia (AAH) has recently been implicated as a precursor to lung adenocarcinoma. We previously reported loss of heterozygosity (LOH) in tuberous sclerosis (TSC) gene-associated regions to frequently be observed in lung adenocarcinoma with multiple AAHs. In this study, we analyzed LOH in four microsatellite loci on 9q, including the TSC1 gene-associated region, and four loci on 16p, including the TSC2 gene-associated region, in both 18 AAHs and 17 concomitant lung adenocarcinomas from 11 patients. 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 loci adjacent to the TSC1 gene. Four of 18 (22%) AAHs and 6 of 17 (35%) adenocarcinomas displayed LOH on 16p. One (6%) AAH and five (29%) adenocarcinomas harbored LOH at loci adjacent to the TSC2 gene. These findings may indicate a causal relationship of LOH on 9q and 16p in a fraction of AAH lesions and adenocarcinomas of the lung. Especially, the frequencies of LOH on 9q and at the TSC1 gene-associated region were high. The TSC1 gene or another neighboring tumor suppressor gene on 9q might be involved in an early stage of the pathogenesis of lung adenocarcinoma.
authors.affiliation: Divsion of Investigative Treatment, National Cancer Center Research Institute East, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takamochi
authors.forename: T
authors.initials: T
authors.lastname: Ogura
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Kurashima
authors.forename: T
authors.initials: T
authors.lastname: Yokose
authors.forename: A
authors.initials: A
authors.lastname: Ochiai
authors.forename: K
authors.initials: K
authors.lastname: Nagai
authors.forename: Y
authors.initials: Y
authors.lastname: Nishiwaki
authors.forename: H
authors.initials: H
authors.lastname: Esumi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D006801:Humans; D006965:Hyperplasia; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology