Next-generation sequencing and identification of additional cancer susceptible genes has made it feasible for patients at risk test for various hereditary cancer syndromes. We have evaluated the performance of a customized multi-gene panel test for hereditary cancer risk assessment in high-risk patients.
A total of 252 patients with multiple primary cancers or high-risk hereditary cancer were identified. Among them, 179 patients (71.0%) had multiple primary cancers, 27 patients (10.7%) were diagnosed bilateral breast cancer younger than 40 years old. Thirty-five patients (13.9%) had 2 ≥ breast cancer family history and 11 patients (4.4%) were very young (≤25 years old) breast cancer patients. Mutations annotated in dbSNP, clinVAR and Ensembl comparative genomic resources were analyzed and reviewed.
In the 65-gene panel test, pathogenic or likely-pathogenic mutations (PM) were identified in 78 (31.0%) patients. Frequency of all PM or likely-PM was 59%, 40%, 26%, and 9% in bilateral breast cancer with ≤ 40 years, breast cancer patients with 2 ≥ family history, multiple primary cancer, and breast cancer patients ≤ 25 years, respectively. The distribution of high-risk genes for hereditary cancer including CDH1, MLH1, MSH2, MSH6, MUTYH, PTEN, TP53, BRCA1, and BRCA2 were 55% in multiple primary cancer patients, 25% in bilateral breast cancer with ≤ 40 years, 18% in breast cancer patients with 2 ≥ family history, and 2% in very young (≤25 years old) breast cancer patients, respectively.
Using a 65-multigene panel test we have identified PMs, especially associated with hereditary cancer. We can use these results for detecting high-risk group of hereditary cancer in breast cancer patients.
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All authors have declared no conflicts of interest.