Mucinous tumours are a group of neoplasms that can arise from multiple organs, including from the gastrointestinal tract and reproductive system. They comprise only a small proportion of tumours at each site and are thus understudied. Less than 3% of epithelial ovarian cancers (OC) are of mucinous histology (mucinous ovarian carcinomas, MOC), and these have distinct genetic and expression changes compared to other OC subtypes. Low-grade MOCs likely progress from benign/borderline precursors, but the development of high-grade MOC is less clear. Questions still remain about whether MOCs are in fact derived from the ovarian tissue itself or represent metastases from distant sites, and this is complicated by difficulties correctly diagnosing primary MOC from extra-ovarian metastases (EOM). Nevertheless, MOCs are an important clinical entity as advanced stage disease is often platinum-resistant with the poorest prognosis among OC, and frequently occurs in young women.
The GAMuT study is an in-depth genomic analysis of mucinous tumours. We aim to (1) identify key events in MOC pathogenesis from benign to fully invasive stages, (2) determine if mucinous cancers share common aberrations regardless of cell of origin and (3) investigate whether molecular genetic or expression changes distinguish between MOC, EOM and primary mucinous tumours from other sites. We are performing exome sequencing, RNAseq and copy number analysis on cases of MOC and EOM identified through CART-WHEEL.org, the AOCS and national and international tissue banks. Established guidelines are being used to aid the diagnosis of primary versus secondary cancers. Genomic data will be compared to that generated for benign and borderline ovarian tumours, and cases pseudomyxoma peritonei and primary non-ovarian mucinous tumours. If mucinous tumours are indeed similar at the genomic level, this finding will change the treatment planning of MOC, by changing chemotherapeutic regimens from ovarian-based to histology-based, and by identifying novel targets for therapy.