Characterization of frequently mutated cancer genes in Chinese breast tumors: a comparison of Chinese and TCGA cohorts
Open accessAbstract
Background: The complexity of breast cancer at the clinical, morphological and genomic levels has been extensively studied in the western population. However, the mutational genomic profiles in Chinese breast cancer patients have not been explored in any detail. Methods: We performed targeted sequencing using a panel consisting of 33 breast cancer-related genes to investigate the genomic landscape of 304 consecutive treatment-naïve Chinese breast cancer patients at Guangdong Provincial People’s Hospital (GDPH), and further compared the results to those in 453 of Caucasian breast cancer patients from The Cancer Genome Atlas (TCGA). Results: The most frequently mutated gene was TP53 (45%), followed by PIK3CA (44%), GATA3 (18%), MAP3K1 (10%), whereas the copy-number amplifications were frequently observed in genes of ERBB2 (24%), MYC (23%), FGFR1 (13%) and CCND1 (10%). Among the 8 most frequently mutated or amplified genes, at least one driver was identifiable in 87.5% (n=267) of our GDPH cohort, revealing the significant contribution of these known driver genes in the development of Chinese breast cancer. Compared to TCGA data, the median age at diagnosis in our cohort was significantly younger (48 vs. 58 years; P<0.001), while the distribution of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) statuses were similar. The largest difference occurred in HR+/HER2- subtype, where 8 of the 10 driver genes compared had statistically significant differences in their frequency, while there were differences in 2 of 10 driver genes among the TNBC and HR+/HER2+ group, but none in the HR-/HER2+ patients in our cohort compared to the TCGA data. Collectively, the most significant genomic difference was a significantly higher prevalence for TP53 and AKT1 in Chinese patients. Additionally, more than half of TP53-mutation HR+/HER2- Chinese patients (~60%) are likely to harbor more severe mutations in TP53, such as nonsense, indels, and splicing mutations. Conclusions: We elucidated the mutational landscape of cancer genes in Chinese breast cancer and further identified significant genomic differences between Asian and Caucasian patients. These results should improve our understanding of pathogenesis and/or metastatic behavior of breast cancer across races/ethnicities, including a better selection of targeted therapies.
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Genetic ancestry may be causally related to some genetic traits and diseases, unlike the social construct of race.
“Fairness and diversity have especially important considerations in such applications given that genetic ancestry may be causally related to some genetic traits and diseases (178, 183-186), as opposed to the social construct of race (173).”
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- Authors
- Zhang, G., Wang, Y., Chen, B., Guo, L., Cao, L., Ren, C., Wen, L., Li, K., Jia, M., Li, C., Mok, H., Chen, X., Wei, G., Lin, J., Zhang, Z., Hou, T., Han-Zhang, H., Liu, C., Liu, H., Liu, J., Balch, C. M., Meric-Bernstam, F., & Liao, N.
- Affiliations
- Guangdong Academy of Medical Sciences (CN)
- Burning Rock Biotech (China) (CN)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Liao, Ning
- ORCID
- Venue
- Annals of Translational Medicine
- Publisher
- AME Publishing Company
- Published
- 2019-04
- Volume
- 7
- Issue
- 8
- Pages
- 179-179
- ISSN
- 2305-5839 (ISSN-L)
- 2305-5847
- PMC
- PMC6526269
- OpenAlex
- W2939142565
- Cited by
- 66
- References
- 52
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 8 · 2022: 12 · 2021: 10 · 2020: 16 · 2019: 3
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Annals of Translational Medicine (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81071851, 81602645, 81001189)
- Natural Science Foundation of Guangdong Province (2018A030313292, 2016A030313768; 2018A030313292, 2016A030313768)
- Guangzhou Municipal Science and Technology Project (201804010430, 201707010418)
- National Cancer Institute (P30CA016672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- breast cancer, mutational landscape, Chinese patients, TP53 mutation, PIK3CA, copy number amplification, driver genes, triple-negative breast cancer, AKT1, TCGA comparison, targeted therapy selection, age at diagnosis, FGFR1, ERBB2, c-Myc
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