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Mutational analysis of key EGFR pathway genes in Chinese breast cancer patients
Lin Tong1, Xue-Xi Yang, Min-Feng Liu
1School of Biotechnology, Breast Center Nanfang Hospital, Southern Medical University, Guangzhou, China.
Background:
The epidermal growth factor receptor (EGFR) is a potential therapeutic target for breast cancer; however, its use does not lead to a marked clinical response. Studies of non-small cell lung cancer and colorectal cancer showed that mutations of genes in the PIK3CA/AKT and RAS/RAF/MEK pathways, two major signalling cascades downstream of EGFR, might predict resistance to EGFR-targeted agents. Therefore, we examined the frequencies of mutations in these key EGFR pathway genes in Chinese breast cancer patients.
Methods:
We used a high-throughput mass-spectrometric based cancer gene mutation profiling platform to detect 22 mutations of the PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes in 120 Chinese women with breast cancer.
Results:
Thirteen mutations were detected in 12 (10%) of the samples, all of which were invasive ductal carcinomas (two stage I, six stage II, three stage III, and one stage IV). These included one mutation (0.83%) in the EGFR gene (rs121913445-rs121913432), three (2.5%) in the KRAS gene (rs121913530, rs112445441), and nine (7.5%) in the PIK3CA gene (rs121913273, rs104886003, and rs121913279). No mutations were found in the AKT1, BRAF, and HRAS genes. Six (27.3%) of the 22 genotyping assays caused mutations in at least one sample and three (50%) of the six assays queried were found to be mutated more than once.
Conclusions:
Mutations in the EGFR pathway occurred in a small fraction of Chinese breast cancers. However, therapeutics targeting these potential predictive markers should be investigated in depth, especially in Oriental populations.
Insights
Mutations in key epidermal growth factor receptor (EGFR) pathway genes are infrequent in Chinese breast cancer patients. Further investigation of these mutations as predictive markers for targeted therapies is warranted, particularly in Asian populations.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Epidermal growth factor receptor (EGFR) is a potential breast cancer therapeutic target, but clinical responses are often limited.
- Mutations in downstream signaling pathways (PIK3CA/AKT, RAS/RAF/MEK) may predict resistance to EGFR-targeted therapies, as observed in other cancers.
- Investigating these key gene mutations in Chinese breast cancer patients is crucial for understanding treatment resistance.
Purpose of the Study:
- To determine the frequency of mutations in critical epidermal growth factor receptor (EGFR) pathway genes.
- To analyze mutations in PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes in Chinese breast cancer patients.
- To explore potential predictive markers for EGFR-targeted therapies in this population.
Main Methods:
- Employed a high-throughput mass-spectrometric based cancer gene mutation profiling platform.
- Detected 22 specific mutations across PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes.
- Analyzed samples from 120 Chinese women diagnosed with breast cancer.
Main Results:
- Mutations were detected in 12 out of 120 (10%) samples, all invasive ductal carcinomas.
- Specific mutations found included PIK3CA (7.5%), KRAS (2.5%), and EGFR (0.83%).
- No mutations were observed in AKT1, BRAF, or HRAS genes.
Conclusions:
- Mutations within the EGFR pathway represent a small subset of Chinese breast cancers.
- Targeted therapeutics focusing on these identified mutations require further in-depth investigation.
- Special attention should be given to Oriental populations for developing and testing these potential predictive markers.
