Homologous recombination deficiency status-based classification of high-grade serous ovarian carcinoma
| Autor: | Masaki Mandai, Noriomi Matsumura, Hidekatsu Nakai, Shiro Takamatsu, Hisamitsu Takaya |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Oncology
medicine.medical_specialty lcsh:Medicine Loss of Heterozygosity Allelic Imbalance medicine.disease_cause Article Epigenesis Genetic Loss of heterozygosity Atlases as Topic Ovarian cancer Terminology as Topic Internal medicine Ovarian carcinoma Cancer genomics medicine Humans Epigenetics Precision Medicine lcsh:Science BRCA2 Protein Ovarian Neoplasms Multidisciplinary BRCA1 Protein business.industry lcsh:R Recombinational DNA Repair DNA Neoplasm Middle Aged Prognosis Debulking Survival Analysis Cystadenocarcinoma Serous Gene Expression Regulation Neoplastic Serous fluid Mutation lcsh:Q Female Neoplasm Grading Homologous Recombination Deficiency Carcinogenesis business |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-8 (2020) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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