The real-world BRCA1/2 germline mutations in Chinese solid tumors.

Authors

null

Jian Chen

The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China

Jian Chen , Zhaohua Gong , Dengjun Sun , Shujie Song , Weiwei Zhang , Ningning Luo , Qin Zhang , Guanghua Lu , Yingxue Qi , Yaqing Wu

Organizations

The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China, The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing Simcere Medical Laboratory Science Co., Ltd, The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, China, The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China

Research Funding

No funding received
None

Background: Breast cancer susceptibility genes BRCA1 and 2 are tumor suppressor genes and they play an important role in DNA damage response and repair during homologous recombination. Hereditary breast and ovarian cancer (HBOC) syndrome is an autosomal dominant disease due to BRCA1 and 2 germline mutation. Germline mutations of BRCA1 and 2 genes significantly increase the risk of developing breast cancer, ovarian cancer, prostate cancer and a broad range of cancers. PARP inhibitor (PARPi) monotherapy and combinations have shown promising efficacy against a variety of cancer types with BRCA mutations. Nevertheless, the knowledge of incidence of BRCA1 and 2 germline mutations in solid tumor remains poorly understood. Herein, next generation sequencing of 539-gene profiling was performed to explore the incidence of BRCA1 and 2 germline mutations in Chinese solid tumors. Methods: We retrospectively analyzed the BRCA1 and BRCA2 germline mutations from a comprehensive 539-gene profiling of 8535 Chinese patients with pan-cancer. 539-gene profiling contains the somatic mutations in tumor tissue or blood ctDNA and the germline mutations in blood leukocyte. We screened out the pathogenic and likely pathogenic mutations in BRCA germline mutations, and calculated the mutation frequency and the median age in every cancer type. Results: In 8535 patients with pan-cancer, 110 patients were found pathogenic or likely pathogenic germline mutations in BRCA gene and the mutation frequency was 1.29%, of which 40 BRCA1 mutations and 70 BRCA2 mutations were found in patients, respectively. The total median age was 58.15. Eliminated a few types of cancers that had a smaller number (less than 50), the higher frequency of mutations contained ovarian cancer (14.78%, media age 58), prostatic cancer (6%, media age 58.33), breast cancer (5.2% media age 57.33). The details of the top 8 cancer types with mutation frequency and media age were shown in Table. Conclusions: This was the first report of the incidence of BRCA1 and 2 germline mutations in Chinese solid tumors, which expanded the understanding of BRCA1/2 and provided a direction for clinical trial design of PARPi monotherapy and combinations.

The mutation frequency and media age of top 8 cancer types (Number≥100).

Cancer type
Number
BRCA1

(%)
BRCA2

(%)
BRCA1/2

(%)
Media age
Ovarian cancer
115
10 (8.70%)
7 (6.08%)
17 (14.78%)
58
Breast cancer
173
6 (3.47%)
3 (1.73%)
9 (5.20%)
57.33
Cholangiocarcinoma
263
2 (0.76%)
6 (2.28%)
8 (3.04%)
65.88
Pancreatic cancer
272
2 (0.74%)
4 (1.47%)
6 (2.21%)
58.83
Esophagus cancer
129
2 (1.55%)
0 (0%)
2 (1.55%)
61
Glioma
134
0 (0%)
2 (1.49%)
2 (1.49%)
51
Lung cancer
3541
11 (0.31%)
26 (0.73%)
37 (1.04%)
58.73
Colorectal cancer
722
0 (0%)
6 (0.83%)
6 (0.83%)
52
Total
8535
40 (0.47%)
70 (0.82%)
110 (1.29%)
58.15

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Publication Only: Prevention, Risk Reduction, and Hereditary Cancer

Track

Prevention, Risk Reduction, and Genetics

Sub Track

Cancer Genetics

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr e22500)

DOI

10.1200/JCO.2021.39.15_suppl.e22500

Abstract #

e22500

Abstract Disclosures

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