Abstract 853P
Background
The DNA damage repair (DDR) is one of the major mechanisms used to maintain genomic integrity. DNA repair deficiency has been recognized as a major hallmark of epithelial ovarian cancer (EOC). However, there is limit data on DDR gene mutation of EOC in Chinese patients. We performed a comprehensive analysis of the germline DDR variants of Chinese EOC patients.
Methods
Next-generation sequencing (NGS) of whole blood samples was conducted using a 36-gene panel in patients with histologically confirmed epithelial ovarian carcinoma, fallopian tube carcinoma or primary peritoneal cancer. The 36-gene panel included 28 homologous recombination repair (HRR) genes, 4 mismatch repair (MMR) genes and 3 other genes related to hereditary tumor.
Results
In total, 110 germline mutations (including only likely pathogenic and pathogenic variant carriers) in DDR genes were observed in 450 EOC patients. Of the 450 EOC patients, 107 patients (23.8%) were gBRCAm carriers, and 32 patients (7.1%) were other germline DDR genes mutation carriers. Frameshift and nonsense variants were the most common deleterious types. The most common mutation in our study other than BRCA1/2 was RAD51D c.270_271dup (n = 8). Most of the gBRCA1m carriers were diagnosed in the age group of 40-59, while most of the gBRCA2m carriers were in the age group of 50-69. The gRAD51Dm carriers were all over 40 years old at the time of diagnosis. Table: 853P
| Genes | Mutation rates |
| BRCA1 | 18.2% |
| BRCA2 | 5.8% |
| RAD51D | 2.4% |
| BRIP1 | 0.7% |
| ATM | 0.4% |
| FANCI | 0.4% |
| MSH2 | 0.4% |
| RAD50 | 0.4% |
| RAD54B | 0.4% |
| RAD54L | 0.4% |
| ATR | 0.2% |
| CHEK2 | 0.2% |
| FANCA | 0.2% |
| FANCD2 | 0.2% |
| NBN | 0.2% |
| PALB2 | 0.2% |
| TP53 | 0.2% |
Conclusions
This study revealed a comprehensive spectrum of DDR germline mutations of epithelial ovarian cancer in China. The major germline mutation of DDR genes in Chinese EOC patients was BRCA1, BRCA2, RAD51D and BRIP1. In agreement with previous studies of BRCA risks in epithelial ovarian cancer, the diagnosis age of BRCA1 mutation carriers was 10 years younger than that of BRCA2 carriers in China. RAD51D c.270_271dup mutation may be enriched in Chinese EOC populations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Chinese Academy of Medical Sciences.
Disclosure
All authors have declared no conflicts of interest.