Japanese nationwide observational multicenter study of tumor BRCA1/2 variant testing in advanced ovarian cancer

Katsutoshi Oda, Daisuke Aoki, Hitoshi Tsuda, Hiroshi Nishihara, Hisanori Aoyama, Hyoe Inomata, Muneaki Shimada, Takayuki Enomoto

Research output: Contribution to journalArticlepeer-review


The association between germline BRCA1 and BRCA2 pathogenic variants (mutations: gBRCAm) and ovarian cancer risk is well established. Germline testing alone cannot detect somatic BRCA1/2 pathogenic variants (sBRCAm), which is calculated based on the proportion of tumor BRCAm (tBRCAm) from tumor samples and gBRCAm. Homologous recombination deficiency (HRD) results mainly from genetic/epigenetic alterations in homologous recombination repair-related genes and can be evaluated by genomic instability status. In Japan, the prevalence of tBRCAm, sBRCAm, and HRD remains unclear. This multicenter, cross-sectional, observational study, CHaRacterIzing the croSs-secTional approach to invEstigate the prevaLence of tissue BRCA1/2 mutations in newLy diagnosEd advanced ovarian cancer patients (CHRISTELLE), evaluated the prevalence of tBRCAm, sBRCAm, and HRD in tumor specimens from newly diagnosed patients with ovarian cancer who underwent gBRCA testing. Of the 205 patients analyzed, 26.8% had a tBRCAm, including tBRCA1m (17.6%) and tBRCA2m (9.3%). The overall prevalence of tBRCAm, gBRCAm, sBRCAm, and HRD-positive status was 26.8%, 21.5%, 6.3%, and 60.0%, respectively. The calculated sBRCAm/tBRCAm ratio was 23.6% (13/55), and the prevalence of gBRCA variant of uncertain significance was 3.9%. These results suggest gBRCA testing alone cannot clearly identify the best course of treatment, highlighting the importance of sBRCA testing in Japan. The present results also suggest that testing for tBRCA and HRD should be encouraged in advanced ovarian cancer patients to drive precision medicine.

Original languageEnglish
Pages (from-to)271-280
Number of pages10
JournalCancer science
Issue number1
Publication statusPublished - 2023 Jan
Externally publishedYes


  • BRCA
  • epithelial ovarian cancer
  • genetic testing
  • germline pathogenic variant
  • homologous recombination

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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