Poster Presentation 25th Lorne Cancer Conference 2013

Genomic profiling of primary mucinous ovarian carcinomas (#336)

Georgie L Ryland 1 2 , Sally M Hunter 1 , Maria A Doyle 3 , Simone M Rowley 1 , Michael Christie 4 , Prue E Allan 5 , Kylie L Gorringe 1 , Ian G Campbell 1
  1. VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
  2. Centre for Cancer Research, Monash Institute of Medical Research, Clayton, Victoria, Australia
  3. Bioinformatics Core Facility, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
  4. Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville, Victoria, Australia
  5. Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia

Mucinous ovarian carcinomas are a clinically important histological subtype of epithelial ovarian cancer with refractory responses to standard ovarian chemotherapeutic regimes leading to poor overall survival. These carcinomas are thought to arise through a stepwise progression from benign cystadenomas to borderline tumours to primary invasive carcinomas, although few studies have comprehensively characterized the genetic changes specific to this subtype or its precursors. Whole exome sequencing identified frequent homozygous inactivating mutations in the novel tumour suppressor gene RNF43 in 9% of borderline precursors and 21% of invasive cases. Furthermore, integration of somatic mutation data with genome-wide copy number alterations revealed that CDKN2A/p16 loss concurrently with MAPK pathway activation is a highly recurrent event which occurs early during mucinous tumour development. Conversely, TP53 mutations were observed at a higher frequency in mucinous carcinomas, suggesting that p53 aberration is associated with progression to invasion. Analysis of additional genetic events common to precursor lesions and invasive disease may lead to the identification of novel pathways associated with mucinous tumour development, some of which may constitute new therapeutic targets for this poorly managed ovarian subtype. In addition, these genetic events may represent novel areas for investigation in tumours with a mucinous histology arising at other organ sites.