Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2 Mutation

Ju Won Kim, Hyo Eun Kang, Jimi Choi, Seung Gyu Yun, Seung Pil Jung, Soo Yeon Bae, Ji Young You, Yoon Ji Choi, Yeul Hong Kim, Kyong Hwa Park

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Purpose BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants. Materials and Methods Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity. Results A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w. Conclusion We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.

Original languageEnglish
Pages (from-to)155-166
Number of pages12
JournalCancer Research and Treatment
Issue number1
Publication statusPublished - 2023 Jan
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2023 by the Korean Cancer Association.


  • BRCA
  • Breast neoplasms
  • Genomic landscape
  • Germ-line mutation
  • High-throughput nucleotide sequencing
  • Tumor mutation burden

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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