GENETIC CHANGES IN OVARIAN-CANCER

The development of cancer is a multistep process involving accumulatio n of genetic changes which progressively transform normal cells to neo plastic cells. During the last few years, our understanding and knowle dge of the genetic changes involved in ovarian carcinogenesis have inc reased dramatically. In this review I will focus on karyotypic abnorma lities in ovarian cancer and will also refer to molecular studies invo lving alterations in oncogenes and tumour suppressor genes in ovarian tumorigenesis. Cytogenetic analyses have identified two distinct subgr oups. Simple karyotypic changes, trisomy 12 being the most common aber ration in this group, are recurrently found in well differentiated ova rian carcinomas. Complex karyotypic abnormalities, including predomina ntly chromosome losses, deletions and unbalanced translocations, are f ound in moderately and poorly differentiated carcinomas. The bands and regions most commonly involved in structural rearrangements have been , in decreasing order of frequency, 19p13, 1p36, 1q21, 1q23-25, 3p11-1 3, 6q21, 19q13, 11p13-15, 11q13, 11q23, 12q24, 12p11-13, and 7p13-22. The finding of identical karyotypic and other genetic changes in tumou r samples taken from different sites, such as tumours from both ovarie s and omental metastases, indicate that ovarian cancer is of unicentri c origin with subsequent metastatic spread giving rise to multiple imp lants. Molecular genetic changes important in ovarian cancer involve b oth classes of tumour-associated genes: oncogenes and tumour suppresso r genes. In contrast to other tumour types, RAS activation is generall y not observed in ovarian cancer. Alterations of MYC1, ERBB2, AKT2, an d TP53 has been described in some ovarian carcinomas. The temporal rel ationship of these mutations, i.e. early or late events in ovarian car cinogenesis, remains to be determined.