Matching maternal isodisomy in mucinous carcinomas and associated ovarian teratomas provides evidence of germ cell derivation for some mucinous ovarian tumors

The tissue derivation of mucinous ovarian carcinoma remains a mystery; however, rare tumors are associated with mature teratoma. Two decades ago, studies of chromosomal heteromorphisms and DNA polymorphisms proved that ovarian teratomas arise during female gametogenesis. We sought to exploit the relationship between mucinous carcinoma and associated teratoma to provide molecular evidence for tissue of origin. Seventeen cases of mucinous ovarian carcinoma were studied, 6 of which had associated mature teratoma. DNA was extracted from the mucinous carcinoma, teratoma, and normal dissected tissue from formalin-fixed, paraffin-embedded sections. Twelve polymorphic microsatellite markers were used to allelotype each sample. Alleles from the teratomas and carcinomas were scored as homozygous (1 allele present in the tumor when normal tissue was heterozygous), heterozygous (2 alleles present matching normal tissue), or noninformative (normal tissue was homozygous). Of the 6 carcinoma/teratoma pairs, 2 showed complete matching homozygosity for informative markers (isodisomy), whereas 2 showed matching heterozygosity. One case did not have the corresponding teratoma available for comparison but demonstrated complete homozygosity and was presumed to be isodisomic. The remaining case had a teratoma homozygous for 7 of 10 informative markers, whereas the matching carcinoma was homozygous for only 2 of these markers. Carcinomas without associated teratoma demonstrated variable zygosity. Microsatellite polymorphism analysis demonstrates that mucinous ovarian carcinomas usually clonally match associated teratomas when present and often show evidence of complete isodisomy, indicating that at least some mucinous carcinomas arise from female gametes and thus are of germ cell origin. The zygosity patterns in mucinous carcinomas without teratoma suggest that these tumors may arise through a different mechanism.