Objective: The goal of this study was to assess the involvement of chromosome 1p deletion in ovarian papillary serous carcinoma (OPSC) via high-resolution physical mapping to detect a candidate tumor suppressor gene previously implicated in uterine papillary serous carcinoma (UPSC) tumorigenesis.
Methods: Previous studies have demonstrated a high rate of loss of heterozygosity (LOH) within a critical region of chromosome 1p in UPSC, suggesting the presence of a putative tumor suppressor gene important in the development of UPSC. To compare the genetic changes in OPSC with those in UPSC, seven microsatellite repeat polymorphisms were used to evaluate LOH in primary OPSC specimens. Allelic intensity was compared between normal and tumor DNA from microdissected, formalin-fixed, paraffin-embedded specimens. In addition to the same seven 1p markers used for UPSC, three additional non-1p markers for chromosomes 1q, 11q, and 2p were tested to determine a baseline rate of LOH.
Results: Overall, 26.6% (8/30) of OPSC (vs 63.2% of UPSC) were characterized by loss at either of the two loci that define the critical region for UPSC. Rates of LOH at each of the 1p loci in the OPSC tumors ranged from 5.6 to 38.9%, which are compatible with background rates of loss for OPSC. LOH at non-1p loci was 29.2%.
Conclusion: While a tumor suppressor gene on 1p appears to be an important genetic event in the development of UPSC, a similar rate and pattern of loss on 1p are not identified in OPSC. Thus, despite the striking clinical similarities between UPSC and OPSC, tumorigenesis in these carcinomas appears to occur via distinctly different pathways.
Copyright 2001 Academic Press.