Mutational Analysis of Triple-Negative Breast Cancer Using Targeted Kinome Sequencing
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Updated: Sep 21, 2025
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Tae-Kyung Yoo1, Woo Seung Lee2, Jisun Kim3
1Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Purpose:
Triple-negative breast cancer (TNBC) does not have defined therapeutic targets and is currently treated with chemotherapy only. Kinase dysregulation triggers cancer cell proliferation and metastasis and is a crucial therapeutic target for cancer. In this study, targeted kinome sequencing of TNBC tumors was performed to assess the association between kinome gene alterations and disease outcomes in TNBC.
Methods:
A kinome gene panel consisting of 612 genes was used for the targeted sequencing of 166 TNBC samples and matched normal tissues. Analyses of the significantly mutated genes were performed. Genomic differences between Asian and non-Asian patients with TNBC were evaluated using two Asian TNBC datasets (from Seoul National University Hospital [SNUH] and Fudan University Shanghai Cancer Center [FUSCC]) and three non-Asian TNBC datasets (The Cancer Genome Atlas [TCGA], METABRIC, and Gustave Roussy). The prognostic value of kinome gene mutations was evaluated using tumor mutational burden (TMB) and oncogenic pathway analyses. Mutational profiles from the TCGA were used for validation.
Results:
The significantly mutated genes included TP53 (60% of patients), PIK3CA (21%), BRCA2 (8%), and ATM (8%). Compared with data from non-Asian public databases, the mutation rates of PIK3CA p.H1047R/Q were significantly higher in the SNUH cohort (p = 0.003, 0.048, and 0.032, respectively). This was verified using the FUSCC dataset (p = 0.003, 0.078, and 0.05, respectively). The TMB-high group showed a trend toward longer progression-free survival in our cohort and the TCGA TNBC cohort (p = 0.041 and 0.195, respectively). Kinome gene alterations in the Wnt pathway in patients with TNBC were associated with poor survival in both datasets (p = 0.002 and 0.003, respectively).
Conclusion:
Comprehensive analyses of kinome gene alterations in TNBC revealed genomic alterations that offer therapeutic targets and should help identify high-risk patients more precisely in future studies.
Insights
Targeted kinome sequencing in triple-negative breast cancer (TNBC) identified key gene alterations like TP53 and PIK3CA. These findings offer potential therapeutic targets and improved patient risk stratification for TNBC.
Area of Science:
- Oncology
- Genomics
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies, relying solely on chemotherapy.
- Kinase dysregulation is a driver of cancer proliferation and metastasis, presenting a therapeutic target.
Purpose of the Study:
- To assess the association between kinome gene alterations and disease outcomes in TNBC.
- To identify potential therapeutic targets for TNBC through kinome sequencing.
Main Methods:
- Targeted sequencing of a 612-gene kinome panel in 166 TNBC samples and matched normal tissues.
- Comparative genomic analysis of Asian and non-Asian TNBC datasets.
- Prognostic evaluation using tumor mutational burden (TMB) and oncogenic pathway analyses.
Main Results:
- Significantly mutated genes identified: TP53 (60%), PIK3CA (21%), BRCA2 (8%), and ATM (8%).
- Higher mutation rates of PIK3CA p.H1047R/Q observed in Asian cohorts (SNUH, FUSCC) compared to non-Asian databases.
- Wnt pathway alterations in TNBC were associated with poor survival.
Conclusions:
- Comprehensive kinome analysis reveals actionable genomic alterations in TNBC.
- Identified alterations can serve as potential therapeutic targets.
- Findings aid in more precise identification of high-risk TNBC patients for future studies.
