Genome-wide single nucleotide polymorphism (SNP) arrays as a novel diagnostic tool in synchronous carcinomas.

Abstract

5105 Background: Synchronous cancers involving ovaries as well as uterine corpus are well-known events in gynecologic malignancies. These tumors may be independently derived, non-metastatic tumors (dual primary tumors; DP) or a tumor from one organ with metastasis to the other (single primary tumor with Metastasis; SPM). In the majority of these synchronous cancers, both tumors are histologically endometrioid adenocarcinomas, which may cause a diagnostic difficulty to distinguish DP and SPM. By genome-wide single nucleotide polymorphism (SNP) arrays, we can obtain chromosomal copy number alterations (CNA) throughout the genome in a single assay. We hypothesized the CNA by SNP arrays might be highly informative for genetic diagnosis in the synchronous endometrioid adenocarcinomas. Methods: We genetically diagnosed ten tumors from five patients with synchronous endometrial and ovarian carcinomas, using 250K SNP typing arrays and mutational analysis of PIK3CA, PTEN, K-Ras and CTNNB1under informed consent and institutional reveiw board approval. We evaluated whether conventional pathological diagnosis is compatible with the genetic diagnosis. Results: Three of the five patients show identical CNA, including type, loci and degree of each alteration, between the endometrial and the ovarian carcinomas. The other two show CNA only in either endometrial or ovarian carcinoma. All the five tumors possess one or more genetic mutations in the genes examined. One patient showed mutations both in PIK3CA and PTEN at discordant sites between endometrial and ovarian carcinomas, whereas the other four showed concordant mutations. Together, four of the five were genetically diagnosed as SPM and the remaining one was as DP. The pathological diagnosis was not in agreement with the molecular diagnosis in four of the five cases. Conclusions: Our data suggest that most of the copy number alterations might occur before metastases and that genome-wide genotyping may represent a useful approach to distinguish between SPM and DP in synchronous endometrial and and ovarian carcinomas. As chromosomal instability is commonly observed, SNP array genotyping might be applicable to synchronous tumors in other organs.