Most Common Mutation in Lung Adenocarcinoma
The most common oncogenic mutation in lung adenocarcinoma varies significantly by ethnicity: EGFR mutations predominate in Asian populations (39-63% of cases), while KRAS mutations are most frequent in Western populations (20-31% of cases). 1, 2
Geographic and Ethnic Variation
The answer to this question fundamentally depends on the patient population being considered:
Asian Populations
- EGFR mutations are the most common driver alteration, occurring in 39.0-63.1% of Chinese patients with lung adenocarcinoma 1, 2
- In one Chinese cohort of 1,356 lung adenocarcinoma patients, EGFR mutations accounted for 63.1% of cases 1
- KRAS mutations occur in only 8.0-10.3% of Asian patients with lung adenocarcinoma 1
Western Populations
- KRAS mutations are the most common driver mutation in Western populations, occurring in approximately 20-31% of lung adenocarcinomas 2, 3, 4
- Multiple studies confirm KRAS as the most frequent oncogenic driver in Western cohorts, with the Lung Cancer Mutation Consortium reporting 27% prevalence 4
- EGFR mutations occur in only 5-20% of white patients 1
Clinical Context for Testing
The 2023 ESMO guidelines emphasize that biomarker testing is essential to identify therapeutically targetable oncogenic drivers, which are mainly found in lung adenocarcinomas 1
Key Testing Considerations:
- EGFR, KRAS, and ALK alterations are typically mutually exclusive, supporting distinct pathogenic pathways 2
- Sequential testing beginning with either KRAS or EGFR is reasonable, as a positive KRAS result obviates the need for EGFR testing (KRAS-mutant tumors are resistant to EGFR TKIs) 1
- Complete sequencing of EGFR exons 18-21 by next-generation sequencing is strongly recommended when EGFR testing is performed 1
Therapeutic Implications
Understanding the most common mutation matters because it directly impacts treatment selection:
- EGFR-mutant tumors respond to EGFR tyrosine kinase inhibitors with response rates of 55-80% 2
- KRAS-mutant tumors are resistant to EGFR TKIs and require alternative strategies 2, 5
- The recent approval of KRAS G12C-specific inhibitors (sotorasib, adagrasib) makes identification of this specific KRAS subtype clinically actionable 3
Common Pitfalls
- Do not assume EGFR is most common globally—this is only true in Asian populations 1, 2
- Do not test for EGFR by FISH or immunohistochemistry—these have no clinical utility 1
- Recognize that approximately 30% of KRAS-mutant patients may harbor additional oncogenic drivers, challenging the mutual exclusivity paradigm 4