Analysis of the TGF beta functional pathway in epithelial ovarian carcinoma

Epithelial ovarian carcinoma is often diagnosed at an advanced stage of disease and is the leading cause of death from gynaecological neoplasia. The genetic changes that occur during the development of this carcinoma are poorly understood. It has been proposed that IGFIIR, TGFbeta1 and TGFbetaRII act as a functional unit in the TGFbeta growth inhibitory pathway, and that somatic loss-of-function mutations in any one of these genes could lead to disruption of the pathway and subsequent loss of cell cycle control. We have examined these 3 genes in 25 epithelial ovarian carcinomas using single-stranded conformational polymorphism analysis and DNA sequence analysis. A total of 3 somatic missense mutations were found in the TGFbetaRII gene, but none in IGFRII or TGFbeta1. An association was found between TGFbetaRII mutations and histology, with 2 out of 3 clear cell carcinomas having TGFbetaRII mutations. This data supports other evidence from mutational analysis of the PTEN and beta-catenin genes that there are distinct developmental pathways responsible for the progression of different epithelial ovarian cancer histologic subtypes.