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Cancer Research and Treatment > Accepted Articles
doi: https://doi.org/10.4143/crt.2021.1567    [Accepted]
Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2 Mutation
Ju Won Kim1 , Hyo Eun Kang2, Jimi Choi3, Seung Gyu Yun4, Seung Pil Jung5, Soo Yeon Bae5, Ji Young You5, Yoon-Ji Choi1, Yeul Hong Kim1, Kyong Hwa Park1
1Division of Medical Oncology and Hematology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
2K-MASTER Cancer Precision Medicine Diagnosis and Treatment Enterprise, Korea University Medical Center, Seoul, Korea
3Division of Endocrinology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
4Department of Laboratory Medicine, Korea University Anam Hospital, Seoul, Korea
5Department of Breast Surgery, Korea University Anam Hospital, Seoul, Korea
Correspondence  Kyong Hwa Park ,Tel: 82-2-920-6841, Fax: 82-2-920-4534, Email: khpark@korea.ac.kr
Received: December 7, 2021;  Accepted: June 6, 2022.  Published online: June 8, 2022.
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.
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 (VUS; 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 (SNVs) 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.
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.
Key words: Breast neoplasms, BRCA, NGS, Germ-line mutation, Genomic landscape, TMB
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