Author of

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  P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12404

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    P3.02-018 - EGFR mutation and its subtypes in Indian population: a study from single academic centre- Tata Memorial Centre (ID 2965)

    09:30 - 09:30  |  Author(s): A. Dutt
    • Abstract

    Background
    Tyrosine Kinase (TK) domains are central regulators of signaling pathways that control differentiation, transcription, cell cycle progression, apoptosis, motility and invasion. EGFR TK mutations represent bona fide somatic mutations in NSCLC. Patients with specific mutations respond better to targeted therapy.Mutation analysis is known to be evaluated by several methods. Real time PCR using allele specific TaqMan primer probes is a simple, robust, highly sensitive, and selective method that is compatible with standard processes used for known gene expression analysis. The main objective of our study was to detect EGFR mutations in NSCLC patients registered in Tata Memorial Hospital (TMH) by using rapid and sensitive technique of RQ-PCR with In-house TaqMan primer probes. There is limited data regarding EGFR mutation in Indian population with variable mutation rate reported. This is an attempt to get actual mutation rate in our population, correlate the frequency of EGFR mutation and their subtypes and analyze across different variables of age, gender, habits and histology with different ethnicity groups.

    Methods
    1018 patients of NSCLC were referred for EFGR testing as a routine service over a 1.5-year period. Extracted DNA from FFPE blocks was amplified for the exons 18, 19, 20 and 21 using the specific TaqMan primer probes with the End point genotyping method on LC-480 II platform. Chi-square test was performed to reveal any significant correlation between the mutation status and age, gender and habits of the patient and tumor histology.

    Results
    Overall Mutation Rate (MR) was 25.0% with a higher mutation rate in females than males (34 vs.21) with a p value of 0.002. Within the age group, MR was high in > 60 yrs group as compared to <60 years (47.6 % vs. 31%). Total population of smoker vs. never-smoker was 37.5% vs. 58.6 %. (p value <0.001). MR was significantly higher in Never Smoker (NS) as compared to Smoker (S) (31.5 % vs.16 %), MR in Adenocarcinoma (ADC) was significantly higher than squamous (27.7 %vs. 5.6%) with a p value of <0.001. MR is higher in ADC NS female as compared to ADC NS male (37.2 %vs.29 %). MR of Exon 19 , 21, 18, & 20 was 53%, 38 %, 5.8 % & 2.4 % respectively. In the cohort of ADC NS gender, Exon 19 positivity was predominantly higher in male than female (61.8% vs.34 %) , whereas Exon 21 was marginally higher in ADC NS female than male (39 % vs 34 %). Exon 20 expressed 2.4%.

    Conclusion
    There is a heterogenous EGFR MR in diferent geographical population. We are in close association with East Asian countries than Western countries. In our data though the MR is high in NS, 16 % of EGFR MR in smokers is also startling reality. Another possibility of variation in EGFR mutation rate could be due to application of different technologies. Each technique differs in their sensitivity and specifictiy. EGFR tyrosine kinase domain define a new molecular marker for lung carcinoma.