Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2Mutation
- Authors
- Kim, Ju Won; Kang, Hyo Eun; Choi, Jimi; Yun, Seung Gyu; Jung, Seung Pil; Bae, Soo Yeon; You, Ji Young; Choi, Yoon-Ji; Kim, Yeul Hong; Park, Kyong Hwa
- Issue Date
- Jan-2023
- Publisher
- 대한암학회
- Keywords
- Breast neoplasms; BRCA; High-throughput nucleotide sequencing; Germ-line mutation; Genomic landscape; Tumor mutation burden
- Citation
- Cancer Research and Treatment, v.55, no.1, pp 155 - 166
- Pages
- 12
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- Cancer Research and Treatment
- Volume
- 55
- Number
- 1
- Start Page
- 155
- End Page
- 166
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/63173
- DOI
- 10.4143/crt.2021.1567
- ISSN
- 1598-2998
2005-9256
- Abstract
- 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.
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Collections - 2. Clinical Science > Department of Anesthesiology and Pain Medicine > 1. Journal Articles
- 2. Clinical Science > Department of Laboratory Medicine > 1. Journal Articles
- 2. Clinical Science > Department of Medical Oncology and Hematology > 1. Journal Articles
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