Homologous recombination deficiency status-based classification of high-grade serous ovarian carcinoma

• Published in: Scientific reports Vol. 10; no. 1; p. 2757
• Main Authors: Takaya, Hisamitsu, Nakai, Hidekatsu, Takamatsu, Shiro, Mandai, Masaki, Matsumura, Noriomi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.02.2020; Nature Publishing Group
• Subjects: 45/61; 692/4028/67/1517/1709; 692/4028/67/69; Allelic Imbalance; Atlases as Topic; BRCA1 protein; BRCA1 Protein - genetics; BRCA1 Protein - metabolism; BRCA2 Protein - genetics; BRCA2 Protein - metabolism; Chemotherapy; Classification; Cystadenocarcinoma, Serous - diagnosis; Cystadenocarcinoma, Serous - genetics; Cystadenocarcinoma, Serous - mortality; Cystadenocarcinoma, Serous - surgery; DNA, Neoplasm - genetics; DNA, Neoplasm - metabolism; Epigenesis, Genetic; Epigenetics; Female; Gene Expression Regulation, Neoplastic; Genomes; Heterozygosity; Homologous recombination; Homologous recombination repair; Humanities and Social Sciences; Humans; Loss of Heterozygosity; Medical prognosis; Middle Aged; multidisciplinary; Mutation; Neoplasm Grading; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - genetics; Ovarian Neoplasms - mortality; Ovarian Neoplasms - surgery; Platinum; Precision Medicine; Prognosis; Recombinational DNA Repair; Science; Science (multidisciplinary); Surgery; Survival; Survival Analysis; Terminology as Topic; Tumorigenesis
• DOI: 10.1038/s41598-020-59671-3
• ISSN: 2045-2322

Homologous recombination repair (HRR) pathway deficiency (HRD) is involved in the tumorigenesis and progression of high-grade serous ovarian carcinoma (HGSOC) as well as in the sensitivity to platinum chemotherapy drugs. In this study, we obtained data from The Cancer Genome Atlas (TCGA) on HGSOC and identified scores for the loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions, and calculated the HRD score. We then investigated the relationships among the score, genetic/epigenetic alterations in HRR-related genes, and the clinical data. We found that BRCA1/2 mutations were enriched in the group with HRD scores ≥63. Compared with the groups with scores ≤62, this group had a good prognosis; we thus considered HRD scores ≥63 to be the best cutoff point for identifying HRD cases in HGSOC. Classification of HGSOC cases by the HRD status revealed a better prognosis for HRD cases caused by genetic alterations (genetic HRD) than those caused by epigenetic changes and those caused by undetermined reasons (p = 0.0002). Among cases without macroscopic residual tumors after primary debulking surgery, 11 of 12 genetic HRD cases survived after the median observation period of 6.6 years, showing remarkably high survival rates (p = 0.0059). In conclusion, HGSOC can be classified into subtypes with different prognoses according to HRD status. This classification could be useful for personalized HGSOC treatment.