Detection of novel germline mutations in six breast cancer predisposition genes by targeted next-generation sequencing

Hum Mutat. 2018 Oct;39(10):1442-1455. doi: 10.1002/humu.23597. Epub 2018 Aug 2.

Abstract

In this study, a customized amplicon-based target sequencing panel was designed to enrich the whole exon regions of six genes associated with the risk of breast cancer. Targeted next-generation sequencing (NGS) was performed for 146 breast cancer patients (BC), 71 healthy women with a family history of breast cancer (high risk), and 55 healthy women without a family history of cancer (control). Sixteen possible disease-causing mutations on four genes were identified in 20 samples. The percentages of possible disease-causing mutation carriers in the BC group (8.9%) and in the high-risk group (8.5%) were higher than that in the control group (1.8%). The BRCA1 possible disease-causing mutation group had a higher prevalence in family history and triple-negative breast cancer, while the BRCA2 possible disease-causing mutation group was younger and more likely to develop axillary lymph node metastasis (P < 0.05). Among the 146 patients, 47 with a family history of breast cancer were also sequenced with another 14 moderate-risk genes. Three additional possible disease-causing mutations were found on PALB2, CHEK2, and PMS2 genes, respectively. The results demonstrate that the six-gene targeted NGS panel may provide an approach to assess the genetic risk of breast cancer and predict the clinical prognosis of breast cancer patients.

Keywords: breast cancer; clinical-pathological features; germline mutation; next-generation sequencing; predisposition gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Checkpoint Kinase 2 / genetics
  • Computational Biology / methods
  • Exons
  • Fanconi Anemia Complementation Group N Protein / genetics
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2 / genetics
  • Molecular Sequence Annotation
  • Neoplasm Grading
  • Neoplasm Staging
  • Oncogenes*
  • Reproducibility of Results
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • Fanconi Anemia Complementation Group N Protein
  • PALB2 protein, human
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • PMS2 protein, human
  • Mismatch Repair Endonuclease PMS2