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Updated: Jun 21, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases
Katharina Schmid1, Natalie Oehl, Fritz Wrba
1Clinical Institute of Pathology and Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria. katharina.schmid@meduniwien.ac.at
Purpose:
The epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated with different frequencies in non-small cell lung cancer and mutations predict clinical response to EGFR inhibitors. The present study compared the mutational status of EGFR, KRAS, and BRAF in primary tumors with the one in corresponding lymph node metastases.
Experimental Design:
Direct bidirectional sequencing of EGFR gene exons 18 to 21, KRAS gene codons 12/13 and 61 to 68, and BRAF exon 15 was done on 96 paired samples of primary lung adenocarcinomas and corresponding locoregional lymph node metastases. In addition, comparative genomic hybridization analyses in two pairs of corresponding primary and metastatic tumor samples with discordant EGFR mutation status were done.
Results:
Mutations in EGFR, KRAS, and BRAF were observed in 7 (7%), 36 (38%), and 2 (2%) patients, respectively. Interestingly, KRAS mutations were observed in two patients with an EGFR mutation. Mutations in primary tumors and lymph node metastases were identical in 1 of 7 (14%) patients in case of EGFR and 11 of 36 (31%) patients in case of KRAS. One patient harbored different KRAS mutations in primary and corresponding metastatic tumors. Comparative genomic hybridization analysis revealed similar patterns of chromosomal changes, strongly supporting a common clonal origin of primary tumors and metastases.
Conclusions:
The possibility of differences in the mutational status of EGFR, KRAS, BRAF between primary tumors and corresponding lymph node metastases should be considered whenever these mutations are used for the selection of patients for EGFR-directed tyrosine kinase inhibitor therapy.
Insights
EGFR, KRAS, and BRAF mutations in lung cancer primary tumors and lymph node metastases often differ. This finding impacts patient selection for targeted therapies, highlighting the need for careful consideration of mutation status in both primary and metastatic sites.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) and its downstream effectors KRAS and BRAF are frequently mutated in non-small cell lung cancer (NSCLC).
- These mutations influence patient response to EGFR-targeted therapies.
- Understanding the concordance of these mutations between primary tumors and metastases is crucial for effective treatment strategies.
Purpose of the Study:
- To compare the mutational status of EGFR, KRAS, and BRAF in primary NSCLC tumors versus corresponding locoregional lymph node metastases.
- To assess the implications of potential discordance for patient selection in EGFR-inhibitor therapy.
Main Methods:
- Direct bidirectional sequencing of key exons/codons in EGFR, KRAS, and BRAF genes.
- Analysis of 96 paired samples of primary lung adenocarcinomas and associated lymph node metastases.
- Comparative genomic hybridization (CGH) on selected discordant samples to confirm clonal origin.
Main Results:
- Mutations were observed in EGFR (7%), KRAS (38%), and BRAF (2%).
- Identical mutations in primary tumors and metastases were found in 14% of EGFR cases and 31% of KRAS cases.
- CGH analysis supported a common clonal origin for primary tumors and metastases, despite potential mutational differences.
Conclusions:
- Significant differences in EGFR, KRAS, and BRAF mutational status can exist between primary lung tumors and lymph node metastases.
- These discrepancies necessitate careful consideration when using mutation status for patient selection for EGFR-directed tyrosine kinase inhibitor therapy.
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