MICROSATELLITE INSTABILITY AND LOSS OF HETEROZYGOSITY AT THE HMLH1 LOCUS ON CHROMOSOME 3P21 OCCUR IN A SUBSET OF NONSMALL CELL LUNG CARCINOMAS

Microsatellite alterations observed in tumor specimens may reflect gen omic instability due to defective mismatch repair genes. To investigat e whether this occurs in human nonsmall cell lung carcinomas we have a nalyzed microsatellite instability at 5 marker loci and loss of hetero zygosity (LOH) at the hMLH1 locus on chromosome 3p21 using the polymer ase chain reaction. Of a total of 49 nonsmall cell lung carcinomas exa mined, 43% (13 of 30 informative cases) showed LOH at 3p21 and 29% (14 of 49) exhibited microsatellite instability at one or multiple loci. LOH of the mismatch repair gene hMLH1 at 3p21 occurred in 82% (9 of 11 informative cases) of the tumors with microsatellite instability. Thi s suggests that defects in the mismatch repair gene hMLH1 at 3p21 may be involved in microsatellite instability and tumorigenesis of a subse t of nonsmall cell lung carcinomas. However, in those nonsmall cell lu ng carcinomas without microsatellite instability LOH at 3p21 probably involved another tumor suppressor gene(s) in this chromosomal region.