Major finding: Study reports on messenger RNA and microRNA expression, promoter methylation, and DNA copy number in high-grade serous ovarian adenocarcinomas.
Impact: Up to half of these cancers may have aberrations in genes involved in homologous recombination and thus benefit from PARP inhibitors.
Approach: Large-scale analysis of genomic aberrations identifies many genes as potential therapeutic targets.
Identification of disease-associated molecular alterations is critical for the development of targeted therapeutics. The Cancer Genome Atlas Research Network has reported on a large-scale analysis of messenger RNA and microRNA expression, promoter methylation, and DNA copy number in 489 high-grade serous ovarian adenocarcinomas. Nearly all high-grade serous ovarian carcinomas were found to have mutations in p53 as well as several genes mutated at lower frequencies, including CDK12, a kinase involved in regulation of RNA splicing. Gene expression analysis identified 4 distinct subtypes of ovarian cancer. Pathway analyses suggest that homologous recombination is defective in about half of the tumors analyzed, and that NOTCH and FOXM1 signaling are involved in serous ovarian cancer pathophysiology. Additionally, 22 genes for which inhibitors already exist were identified in regions of recurrent amplification.
Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011, 474:609–15.
Note: Research Watch is written by Cancer Discovery Editors. Readers are encouraged to consult the articles referred to in each item for full details on the findings described.