Abstract B11: Mutational heterogeneity in non-serous ovarian cancers.

Background: The mutational landscape of non-serous ovarian carcinomas is underexplored despite their substantial contribution to ovarian cancer morbidity and mortality. In this study we report whole exome sequencing analysis of 10 non-serous ovarian tumors and matched normal samples. We also report targeted gene sequencing results of an additional 28 non-serous tumor samples targeting 1,321 genes selected for their involvement in cancer. Methods: Whole exome capture was performed using Roche NimbleGen SeqCap EZ, followed by sequencing of captured libraries using an Illumina HiScan platform. Target gene capture was performed using SureSelect custom designs, using GAIIx sequencing technology. Sequences from both experimental procedures were aligned to the human genome using the Burrows-Wheeler Aligner and the Genome Analysis ToolKit was used for insertion/deletion realignment, quality score calibration, and variant identification. Mutations were detected with MuTect or Strelka (whole exome) or GATK (target gene). Results: We annotated 32,965 somatic mutations (829-15,737 per tumor) for an overall rate of mutation 12.2 per Mb. Interestingly, a BRCA2 frameshift mutation was observed in mucinous tumors; although inherited BRCA mutations have not been previously observed in mucinous histology. TP53 mutations were much less common than observed in high-grade serous ovarian cancers. PTEN stood out as a gene containing truncating mutations in many samples. We confirmed FOXL2 importance in granulosa, KRAS in mucinous histology and identified POLE mutations in endometrioid ovarian samples. Finally, we report comparative analysis of our results to The Cancer Genome Atlas (TCGA) database. Conclusion: In summary, we report that non-serous ovarian tumors are mutationally distinct from serous ovarian tumors, having a mutational profile more similar to non-serous endometrial cancers. Citation Format: Jaime Teer, Sean Yoder, Anxhela Gjyshi, Chaomei Zhang, Alvaro Monteiro. Mutational heterogeneity in non-serous ovarian cancers. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B11.