OVARIAN-CANCER HAS FREQUENT LOSS OF HETEROZYGOSITY AT CHROMOSOME 112P12.3-13.1 (REGION OF TEL AND KIP1 LOCI) AND CHROMOSOME 12Q23-TER - EVIDENCE FOR 2 NEW TUMOR-SUPPRESSOR GENES

Identification of the key genetic alterations leading to ovarian cance r is in its infancy. Polymerase chain reaction (PCR)-based analysis of loss of heterozygosity (LOH) is a powerful method for detecting regio ns of altered tumour-suppressor genes. Focusing on chromosome 12, we e xamined 23 ovarian cancer samples for LOH using 31 highly polymorphic microsatellite markers and found the chromosomal localization of two p utative tumour-suppressor genes. Two commonly deleted regions were 12p 12.3-13.1 in 6/23 (26%) and 12q23-ter in 7/23 (30%) samples. LOH on ch romosome 12 was more common in late-stage ovarian carcinomas. The regi on of LOH at 12p12.3-13.1 includes the genes that code for the ETS-fam ily transcriptional factor, known as TEL, and the cyclin-dependent kin ase inhibitor, known as p27(Kip1). Mutational analysis of both TEL and p27(Kip1) using single-strand conformation polymorphism (SSCP) showed no abnormalities, suggesting that the altered gene in this region is neither of these genes. Taken together, our data suggest that new tumo ur-suppressor genes in the region of chromosomes 12p12.3-13.1 and 12q2 3-ter may be involved in the development of ovarian cancer.