Common epidermal growth factor receptor mutations in north Indian patients with non-small cell lung carcinoma:
Rakesh Behera1, Sheetal Arora1, Pranav Ish2
1Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi.
Abstract:
Lung carcinoma was the most common cause of cancer deaths globally in 2022, with non-small cell lung carcinoma (NSCLC) accounting for 81% of the burden. Due to promising tyrosine kinase inhibitor (TKI) trials, NSCLC patients harboring EGFR gene mutations are of interest. Our aim was to determine EGFR mutation prevalence in north India and its histologic and demographic correlations. We investigated the frequency of EGFR mutations in 40 patients with histologically confirmed NSCLC using real-time polymerase chain reaction. A 15% mutation frequency was observed in the study sample, involving 32 males and 8 females with a median age of 59 years. Squamous cell carcinoma (SCC) patients had only EXON20 (T790M, exon20 insertion) mutations, while adenocarcinoma patients had mutations in both EXON20 (T790M) and 21 (L858R) with mutation frequencies of 22% and 10%, respectively. 28% of the SCC patients were non-smokers, and 60% of these non-smokers had an EGFR mutation. South Indian and Asian studies have identified EXON19 (19-Del) and EXON21 (L858R) mutations as "common mutations" that account for nearly 80-90% of all mutations and respond well to TKIs. Interestingly, "common mutations" were found seldom in our study population, while the uncommon variants constitute 83% of all mutations, which we assume is due to diverse Indian genetics and ethnicity and co-existing signature mutations that involve the tyrosine kinase domain of EXON20. We suggest future genome-wide association studies to identify plausible genetic polymorphisms responsible for interethnic differences in EGFR mutation, which will contribute to better treatment and prevention of NSCLCs.
Insights
Epidermal growth factor receptor (EGFR) mutations in North Indian non-small cell lung carcinoma (NSCLC) patients were analyzed. Uncommon EGFR mutations were prevalent, differing from common mutations found in other Asian populations, suggesting genetic diversity impacts NSCLC treatment.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Lung carcinoma is a leading global cause of cancer death, with non-small cell lung carcinoma (NSCLC) being the most prevalent type.
- Epidermal growth factor receptor (EGFR) gene mutations are crucial in NSCLC, particularly for patients responding to tyrosine kinase inhibitors (TKIs).
- Understanding EGFR mutation prevalence and patterns in diverse populations like North India is essential for targeted therapy and treatment strategies.
Purpose of the Study:
- To determine the frequency of EGFR mutations in North Indian NSCLC patients.
- To investigate the correlation of EGFR mutations with histological subtypes and demographic factors.
- To compare EGFR mutation patterns in North India with those reported in other Asian populations.
Main Methods:
- Real-time polymerase chain reaction (PCR) was used to analyze EGFR mutations in 40 histologically confirmed NSCLC patients.
- Histological subtypes (squamous cell carcinoma, adenocarcinoma) and demographic data were collected.
- Mutation frequencies were calculated and compared with existing literature.
Main Results:
- A 15% overall EGFR mutation frequency was observed in the study cohort (32 males, 8 females, median age 59).
- Squamous cell carcinoma (SCC) patients exhibited only EXON20 mutations (T790M, exon20 insertion).
- Adenocarcinoma patients showed mutations in EXON20 (T790M) and EXON21 (L858R) with frequencies of 22% and 10%, respectively.
- Uncommon EGFR variants constituted 83% of mutations in this cohort, contrasting with the high prevalence of common mutations (EXON19, EXON21) in other Asian studies.
- A significant proportion (60%) of non-smoking SCC patients had EGFR mutations.
Conclusions:
- The EGFR mutation landscape in North Indian NSCLC differs significantly from other Asian populations, with a higher prevalence of uncommon variants, potentially due to genetic and ethnic diversity.
- The high frequency of EXON20 mutations, particularly in SCC and non-smokers, warrants further investigation.
- Future genome-wide association studies are recommended to identify genetic polymorphisms contributing to these interethnic differences in EGFR mutations, aiding in personalized NSCLC treatment and prevention.
