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 ovarian 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 and evaluated the effect of observed deletions with regard to different clinicopathological variables. LOH was detected in 61% of the patients. Interestingly, LOH for the D11S1340 marker locus at 11q23. 3 seemed to be associated with significantly reduced survival times (P = 0.005) and serous tumor histology (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 simultaneously displayed deletions at two distinct 11q regions, A and B, which are proximal 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 directly associated with a more aggressive disease course. Therefore, it appears that 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 close to D11S1340 at 11q23.3. This corresponds well to our earlier observation in breast cancer, suggesting the involvement of a shared survival factor gene in both diseases.