Molecular genetic defects in endometriosis

In a series of studies, we have hypothesised that endometriotic proliferati on is, in part, precipitated by mutations in oncogenes or deletions in tumo r suppressor genes that have been shown to be important steps in the transf ormation from a benign to a malignant epithelium. We reported previously th at we could find no mutations in the TP53 and RASK genes in cases of endome triosis. However, having shown that endometriotic deposits were monoclonal, we showed loss of heterozygosity on chromosomes 9p (18%), 11q (18%), and 2 2q (15%)- in total 28% of endometriotic lesions showed loss of heterozygosi ty at one or more sites [1]. We could not demonstrate any loss of heterozyg osity in normal endometrium. We examined adjacent endometriosis, atypical e ndometriosis, and endometrioid carcinoma of the ovary and showed common gen etic alterations that are consistent with a common lineage, These common al terations were not seen in lesions that were distant from each other [2]. I n endometrioid tumors, we reported an increased frequency of mutations in t he PTEN/MMAC tumor suppressor genes that was not seen in clear cell or sero us carcinoma, suggesting distinct developmental pathways for these tumors [ 3]. Copyright (C) 2000 S. Karger AG, Basel.