key papersKey paper
Integrated genomic analyses of ovarian carcinoma (The Cancer Genome Atlas)
Sequencing nearly 500 high-grade serous ovarian cancers showed that almost all carry TP53 mutations and about half have defects in homologous recombination DNA repair, the biology that PARP inhibitors exploit.
Overview
Integrated genomic analysis by The Cancer Genome Atlas of 489 high-grade serous ovarian adenocarcinomas, finding TP53 mutations in 96 percent, germline or somatic BRCA1/2 mutations in about 20 percent, homologous recombination defects in about half, widespread copy-number changes, and four transcriptional subtypes.
Translational studyChanged practice489 participants
Authors
Cancer Genome Atlas Research Network.
Published
Nature, 2011
Findings
- TP53 mutated in 96 percent of high-grade serous ovarian cancers.
- Homologous recombination pathway defects in about 50 percent, including BRCA1/2 in about 20 percent.
What it means
The homologous recombination deficiency concept, and the case for testing all high-grade serous cancers for BRCA and related defects, come from this dataset.
Caveats
- Research-grade profiling of primary tumours; clinical homologous recombination deficiency assays came later.