Supplementary Material for: Germline mutations in 32 cancer susceptibility genes by Next-Generation Sequencing among breast cancer patients

Introduction: 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 (NGS) 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 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 (TNBC) patients may be more likely to be recommended for detecting P/LP germline mutations in HRR genes.