Abstract 5107: Unravelling the complexity of individual cancer genomes

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Ovarian cancer affects ∼ 204,000 women each year, and it is one of the leading causes of cancer-related death among women world-wide, as most patients present with advanced stage (III/IV) tumours, and only 40% survive 5 years after diagnosis. Improvement in the clinical management of ovarian patients is likely to derive from a better understanding of the molecular aberrations which initiate and maintain tumour growth as well as from the discovery of novel drug-able targets for the development of personalised targeted therapies. In this study, we comprehensively characterised the cancer genome of a patient diagnosed with grade III serous ovarian carcinoma, using a combination of massive-parallel sequencing technologies, including long distance DNA Paired-End-Tag (DNA-PET) sequencing, RNA-sequencing and exome-capture sequencing. This approach ensures deep coverage (from 50-180X) of critical mutational elements in a cancer genome. By comparing the genomic abnormalities identified in the tumour sample with those found in its normal counterpart (peripheral blood lymphocytes), we were able to compile a catalogue of all of the somatic events which occurred during oncogenesis and to define the overall complexity of this specific cancer genome. Interestingly, chromosomal arm loss appeared to be the predominant feature of this tumour, with more than 30% of the haploid genome being affected by a decrease in copy number. This associated with a prevalence of inter-chromosomal rearrangements, suggesting chromosomal translocations as a preferred consequence of genomic instability. Here we describe some examples of somatic translocation events causing the loss of tumour suppressor genes. Using this genotype as a possible model of ovarian carcinoma evolution, we aim to explain a subset of ovarian cancers displaying a similar chromosomal profile by applying an analysis of copy number variations, and to define common mechanisms of cancer gene loss. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5107. doi:1538-7445.AM2012-5107