A NOVEL 4 CM MINIMAL DELETION UNIT ON CHROMOSOME 6Q25.1-Q25.2 ASSOCIATED WITH HIGH-GRADE INVASIVE EPITHELIAL OVARIAN CARCINOMAS

Detailed deletion mapping of chromosome 6q has shown that the highest percentage of loss of heterozygosity (LOH) is located at 6q25-q27 and suggested that an ovarian cancer associated tumor suppressor gene may reside in this region. To further define the smallest region of common loss, we used 12 tandem repeat markers spanning a region no more than 18 cM, located between 6q25.1 and 6q26, to examine allelic loss in 54 fresh and paraffin embedded invasive ovarian epithelial tumor tissues . Loss of heterozygosity was observed more frequently at the loci defi ned by marker D6S473 (14 of 32 informative cases, 44%) and marker D6S4 48 (17 of 40 informative cases, 43%). Detailed mapping of chromosome 6 q25-q26 in these tumor samples identified a 4 cM minimal region of LOH between markers D6S473 and D6S448 (6q25.1-q25.2). Loss of heterozygos ity at DGS473 correlated significantly both with serous versus non-ser ous ovarian tumors (P=0.040) and with high grade versus low grade spec imens (P=0.023). The results suggest that a 4 chi deletion unit locate d at 6q25.1-q25.2 may contain the putative tumor suppressor gene which may play a role in the development and progression of human invasive epithelial ovarian carcinomas (IEOC).