LOSS OF HETEROZYGOSITY IN THE TUBEROUS SCLEROSIS GENE ASSOCIATED REGIONS IN ADENOCARCINOMA OF THE LUNG ACCOMPANIED BY MULTIPLE ATYPICAL ADENOMATOUS HYPERPLASIA

To investigate the potential allelic loss of tumor suppressor gene loc i in the tuberous sclerosis complex (TSC)-associated regions located o n the long arm of chromosome 9 (9q) and on the short arm of chromosome 16 (16p) in human lung carcinoma, we analyzed 21 paired normal and tu mor DNAs with II polymorphic markers on the chromosomes. All tumors we re adenocarcinoma of the lung, which included 9 adenocarcinomas with a ssociated multiple atypical adenomatous hyperplasia (AAH). A precise m icrodissection technique followed by polymerase chain reaction (PCR) a mplification to prevent under-evaluation of loss of heterozygosity (LO H) was used. Twelve of the 21 (57%) adenocarcinomas displayed LOH on 9 q. Five of the 21 adenocarcinomas (24%) showed LOH at all informative loci on 9q, whereas 7 (33%) demonstrated partial LOH on 9q34. Among th ese 21, 5 (24%) showed partial LOH between D9S149 and D9S150, where TS CI is located. The incidence of associated AAH was significantly highe r in adenocarcinoma harboring a partial LOH in the TSCI-associated reg ion (p = 0.0048). Twelve of the 21 (57%) adenocarcinomas displayed LOH on 16p. No significant differences in the clinico-pathological charac teristics could be discerned between adenocarcinomas with and without LOH on 16p. When combining these data, a partial LOH at TSCI- and/or T SC2-associated loci was observed more frequently in cases with well-di fferentiated adenocarcinoma (p = 0.086) and associated AAH (p = 0.081) . In conclusion, our results suggest that the TSC-associated regions a re new candidate loci for tumor suppressor genes in lung adenocarcinom a, especially when it is accompanied by multiple AAH. Int. J. Cancer ( Pred. Oncol.) 79:384-389, 1998. (C) 1998 Wiley-Liss, Inc.