Chromosome 11q22.3-q25 LOH in ovarian cancer: Association with a more aggressive disease course and involved subregions

Chromosome 11q deletions are common in various malignancies, including ovar ian cancer. However, the clinical significance of these genetic lesions as well as their more precise chromosomal location is largely unknown. Here we have examined epithelial ovarian cancer material from 49 patients for loss of heterozygosity (LOH) using nine microsatellite markers on 11q22.3-q25 a nd evaluated the effect of observed deletions with regard to different clin icopathological variables. LOH was detected in 61% of the patients. Interes tingly, LOH for the D11S1340 marker locus at 11q23.3 seemed to be associate d with significantly reduced survival times (P = 0.005) and serous tumor hi stology (P = 0.036). LOH for D11S912 at the more distal 11q24-q25 location correlated with a higher tumor stage (P = 0.003), serous tumor histology (P = 0.015), and finding of residual tumor (P = 0.047), but not directly with survival times (P = 0.320). The majority of the analyzed tumors simultaneo usly displayed deletions at two distinct 11q regions, A and B, which are pr oximal and distal to D11S1347/NCAM (11q23.2-q23.3), respectively. Only LOH for two markers (D11S1340 and D11S912) of the B region seemed to be directl y associated with a more aggressive disease course. Therefore, it appears t hat deletions of the ataxia telangectasia gene of the A region would not be crucial for determining the outcome of ovarian cancer. Our present results indicate that a survival factor gene in ovarian cancer would be located cl ose to D11S1340 at 11q23.3. This corresponds well to our earlier observatio n in breast cancer, suggesting the involvement of a shared survival factor gene in both diseases. (C) 1998 Academic Press.