IDENTIFICATION OF A NOVEL REGION OF HOMOZYGOUS DELETION ON CHROMOSOME9P IN SQUAMOUS-CELL CARCINOMA OF THE LUNG - THE LOCATION OF A PUTATIVE TUMOR-SUPPRESSOR GENE

Cytogenetic and molecular studies have implied the presence of tumor s uppressor genes (TSGs) on chromosome 9p that are critical in the devel opment of lung and other cancers, The p16/CDKN2 gene, a cyclin depende nt kinase inhibitor, is a well-defined TSG on 9p21, Although the frequ ency of mutations in the p16/CDKN2 gene has been detected in approxima tely 30% of non-small cell lung cancer, loss of heterozygosity on 9p h as been observed in greater than 70% of non-small cell lung cancers, T hese and other deletion mapping studies have suggested the existence o f additional TSGs on 99, This study examined chromosome 99 for TSG loc i by analyzing 23 squamous cell carcinomas of the lung with 21 microsa tellite markers, Loss of heterozygosity was detected in all of the tum ors, and homozygous deletions of the p16/CDKN2 locus were observed in 6 of the 23 tumors (26%), In addition, a novel region of homozygous de letion was detected in six tumors (26%) at D9S126, approximately 2.5 c M proximal to p16/CDKN2, A single tumor contained a homozygous deletio n at both the p16/CDKN2 locus and the D9S126 locus, The possibility of homozygous loss was confirmed by multiplex PCR using both the D9S126 marker and a chromosome 99 control marker, Fluorescence in situ hybrid ization analysis with Pf, and cosmid probes containing D9S126 also con firmed these data, The minimum region of homozygous deletion was deter mined by testing markers immediately proximal and distal to the D9S126 region, The data identify a homozygous loss on the short arm of chrom osome 9 suggesting the presence of a novel TSG locus, proximal to p16/ CDKN2 and located between D9S265 and D9S259.