A molecular genetic analysis of endometriosis and the association with ovarian cancer

The data presented here shows that LOH is a frequent event in endometriosis, both with and without synchronous carcinoma, and solitary endometrioid and clear cell ovarian cancer. In a number of cases of endometriosis with synchronous carcinoma the same genetic alterations were seen, strengthening the case for the two having a common lineage as previously reported.Mutations of the GALT gene, in particular the N314D polymorphism has been previously reported to be frequent in endometriosis and endometrioid carcinomas and postulated to cause the development of subtle vaginal defects which could lead to endometriosis via retrograde menstruation. The data presented here finds an association between GALT mutations and ovarian tumours of the serous and undifferentiated subtypes but not with endometriosis and endometrioid ovarian cancer.The PTEN, β-catenin and VHL genes have been shown to be mutated in a wide range of tumours and previous reports of their role in ovarian cancer has been biased towards studying the more common serous histological subtype. Frequent somatic mutations of the PTEN and β-catenin genes, but not the VHL gene, were found in ovarian cancers. The mutations were restricted to the endometrioid subtype only, an indication that the different histological subtypes of ovarian cancer arise through different pathways. PTEN and VHL were also analysed in a number of cases of endometriosis but nothing was found. As PTEN and β-catenin play integral roles in cell physiology via signalling pathways it would be beneficial to examine how they interact with other components of these pathways to identify other genes which may be capable of producing the tumour phenotype when mutated.