Germline Mutations in 32 Cancer Susceptibility Genes by Next-Generation Sequencing among Breast Cancer Patients. 2024

Yu Yang, and Chang Liu, and Zhong-Ling Zhuo, and Fei Xie, and Ke Wang, and Shu Wang, and Xiao-Tao Zhao
Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.

BACKGROUND BRCA1/2 germline mutations are the most well-known genetic determinants for breast cancer. However, the distribution of germline mutations in non-BRCA1/2 cancer susceptibility genes in Chinese breast cancer patients is unclear. The association between clinical characteristics and germline mutations remains to be explored. METHODS Consecutive breast cancer patients from Peking University People's Hospital were enrolled. Clinical characteristics were collected, and next-generation sequencing was performed using blood samples of participants to identify pathogenic/likely pathogenic (P/LP) germline mutations in 32 cancer susceptibility genes including homologous recombination repair (HRR) genes. RESULTS A total of 885 breast cancer patients underwent the detection of germline mutations. 107 P/LP germline mutations of 17 genes were identified in 116 breast cancer patients including 79 (8.9%) in BRCA1/2 and 40 (4.5%) in 15 non-BRCA1/2 genes. PALB2 was the most frequently mutated gene other than BRCA1/2 but still relatively rare (1.1%). There were 38 novel P/LP germline variants detected. P/LP germline mutations in BRCA1/2 were significantly associated with onset age (p < 0.001), the family history of breast/ovarian cancer (p = 0.010), and molecular subtype (p < 0.001), while being correlated with onset age (p < 0.001), site of breast tumor (p = 0.028), and molecular subtype (p < 0.001) in HRR genes. CONCLUSIONS The multiple-gene panel prominently increased the detection rate of P/LP germline mutations in 32 cancer susceptibility genes compared to BRCA1/2 alone. Onset younger than or equal to 45 years of age, bilateral and triple-negative breast cancer patients may be more likely to be recommended for detecting P/LP germline mutations in HRR genes.

UI MeSH Term Description Entries
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D059014 High-Throughput Nucleotide Sequencing Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc. High-Throughput Sequencing,Illumina Sequencing,Ion Proton Sequencing,Ion Torrent Sequencing,Next-Generation Sequencing,Deep Sequencing,High-Throughput DNA Sequencing,High-Throughput RNA Sequencing,Massively-Parallel Sequencing,Pyrosequencing,DNA Sequencing, High-Throughput,High Throughput DNA Sequencing,High Throughput Nucleotide Sequencing,High Throughput RNA Sequencing,High Throughput Sequencing,Massively Parallel Sequencing,Next Generation Sequencing,Nucleotide Sequencing, High-Throughput,RNA Sequencing, High-Throughput,Sequencing, Deep,Sequencing, High-Throughput,Sequencing, High-Throughput DNA,Sequencing, High-Throughput Nucleotide,Sequencing, High-Throughput RNA,Sequencing, Illumina,Sequencing, Ion Proton,Sequencing, Ion Torrent,Sequencing, Massively-Parallel,Sequencing, Next-Generation
D018095 Germ-Line Mutation Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not. Mutation, Germ-Line,Germline Mutation,Germ Line Mutation,Germ-Line Mutations,Germline Mutations,Mutation, Germ Line,Mutation, Germline,Mutations, Germ-Line,Mutations, Germline
D019313 BRCA1 Protein The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). It contains an N-terminal RING FINGER DOMAIN and is a PROTEIN PHOSPHATASE 1 regulatory subunit. In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91) BRCA1 Gene Product,Breast Cancer 1 Gene Product,Breast Cancer 1 Protein,Breast Cancer Type 1 Susceptibility Protein,Ring Finger Protein 53
D020022 Genetic Predisposition to Disease A latent susceptibility to disease at the genetic level, which may be activated under certain conditions. Genetic Predisposition,Genetic Susceptibility,Predisposition, Genetic,Susceptibility, Genetic,Genetic Predispositions,Genetic Susceptibilities,Predispositions, Genetic,Susceptibilities, Genetic
D024682 BRCA2 Protein A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6) Breast Cancer 2 Gene Product,Fanconi Anemia Complementation Group D1 Protein,BRCA2 Gene Product,Breast Cancer 2 Protein,FANCD1 Protein,Fanconi Anemia Group D1 Complementing Protein,Fanconi Anemia Group D1 Protein
D064726 Triple Negative Breast Neoplasms Breast neoplasms that do not express ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and do not overexpress the NEU RECEPTOR/HER-2 PROTO-ONCOGENE PROTEIN. ER-Negative PR-Negative HER2-Negative Breast Cancer,ER-Negative PR-Negative HER2-Negative Breast Neoplasms,Triple Negative Breast Cancer,Triple-Negative Breast Cancer,Triple-Negative Breast Neoplasm,Breast Cancer, Triple-Negative,Breast Cancers, Triple-Negative,Breast Neoplasm, Triple-Negative,Breast Neoplasms, Triple-Negative,ER Negative PR Negative HER2 Negative Breast Cancer,ER Negative PR Negative HER2 Negative Breast Neoplasms,Triple Negative Breast Neoplasm,Triple-Negative Breast Cancers,Triple-Negative Breast Neoplasms

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