Abstract A3: Mucinous ovarian tumors: Are they all the same?

Abstract

Abstract Background: Mucinous adenocarcinomas (MC) comprise a distinct group of neoplasms that can arise in multiple organs, such as the ovary, pancreas and gastrointestinal tract, but are relatively understudied. Mucinous ovarian carcinomas (MOC) are a distinct histological subtype of epithelial ovarian cancer, with late stage and high-grade MOC often resistant to standard platinum-based ovarian chemotherapeutic regimens. Controversy exists over whether high-grade MOC arise in the ovary or represent metastases from distant sites with secondary ovarian involvement. This study aims to determine if differences exist at the molecular level that distinguish low- and high-grade MOC, mucinous tumours of extra-ovarian origin (EOM) and primary MC from other sites, as this has significant implications for treatment strategies. Methods: We are identifying cases of low- and high-grade MOC from CART-WHEEL.org, the Australian Ovarian Cancer Study and national and international tissue banks. High-resolution molecular characterization of these cases using whole-exome sequencing, copy number arrays and RNAseq will be compared to similar data generated for mucinous cystadenomas and borderline ovarian tumours (the putative precursors to MOC), and cases of EOM, pseudomyxoma peritonei and primary MC from other sites. Results: Copy number analysis and mutation screening (KRAS, BRAF, NRAS, TP53, CDKN2A) of 22 cystadenomas, 22 borderline tumours and 31 MOC has identified activating RAS/RAF pathway mutations concurrent with CDKN2A loss by homozygous deletion, inactivating mutations and loss of heterozygosity as common to all mucinous ovarian tumours, while TP53 mutations were largely restricted to MOC. Exome sequencing of selected cases has revealed additional genes recurrently targeted by deleterious mutations. Conclusions: Preliminary findings demonstrate that the majority of MOC share genomic events with their putative precursors, supporting a cystadenoma-borderline-carcinoma progression for both low- and high-grade MOC. Intriguingly, exome sequencing suggests a significant overlap of mutated genes with mucinous tumours arising from other organ sites, although it remains to be seen whether gene expression analysis can distinguish site of origin for tumours with a mucinous histology. Citation Format: Ian Campbell, Sally Hunter, Wakefield Mathew, Yoland Antill, Susie Bae, Sumitra Ananda, Monique Topp, Lara Lipton, Winston Liauw, Thomas Jobling, Alex Boussioutas, Michael Christie, Prue Allan, Michael Friedlander Michael Friedlander, Stephen Fox, Anna Defazio, David Bowtell, Jan Pyman, Study Australian Ovarian Cancer, Clare Scott, Kylie Gorringe. Mucinous ovarian tumors: Are they all the same? [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A3.