A NOVEL TUMOR-SUPPRESSOR LOCUS ON CHROMOSOME 18Q INVOLVED IN THE DEVELOPMENT OF HUMAN LONG CANCER

The high incidence of loss of heterozygosity (LOH) on chromosome 18q i n advanced non-small cell lung carcinomas indicates the presence of tu mor suppressor gene(s) on this chromosome arm, which plays an importan t role in the acquisition of malignant phenotypes in lung cancers. In the present study, we examined 62 lung cancer specimens and 54 lung ca ncer cell lines for allelic imbalance at 11 microsatellite loci to def ine common regions of 18q deletions. Allelic imbalance of 18q was dete cted in 24 (55.8%) non-small cell lung carcinoma specimens and in 6 (3 1.6%) small cell lung carcinoma specimens, whereas a similar frequency of LOH was statistically inferred Po occur in cell lines by analyzing marker homozygosity as an indirect measure of LON. Five specimens and 11 cell lines showed partial or interstitial deletions of chromosome 18q, and 2 of them had homozygous deletions at the 18q21.1 region. A c ommonly deleted region nas assigned between the D18S46 and gamma 953G1 2R loci. The size of this region is less than 1 Mb, and the coding exo ns of three candidate tumor suppressor genes, Smad2, Smad4, and DCC, w ere mapped outside the region. This result suggests that the common re gion harbors a novel tumor suppressor gene involved in the progression of lung cancer.