Screening for EGFR mutations in lung cancer, a report from India
| Autor: | B S Ajai Kumar, Ashwini Nargund, V. Chitti Babu, V Vidya Harini, Rashmita Sahoo, Geeta V Patil Okaly, S. M. Rao, Raghavendra M Rao, E Venkataswamy |
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| Rok vydání: | 2010 |
| Předmět: |
Pulmonary and Respiratory Medicine
Cancer Research Lung Neoplasms DNA Mutational Analysis Mutation Missense India Single-nucleotide polymorphism medicine.disease_cause Polymorphism Single Nucleotide Erlotinib Hydrochloride Gefitinib Sex Factors Carcinoma Non-Small-Cell Lung medicine Prevalence Missense mutation Humans Epidermal growth factor receptor Lung cancer Sequence Deletion Mutation biology business.industry Age Factors Middle Aged medicine.disease ErbB Receptors Oncology Cancer research biology.protein Quinazolines Erlotinib business medicine.drug |
| Zdroj: | Lung cancer (Amsterdam, Netherlands). 73(3) |
| ISSN: | 1872-8332 |
| Popis: | Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers including the lung malignancy. Genetic modifications such as deletions, insertions and Single Nucleotide Polymorphisms in the tyrosine kinase (TK) domain of EGFR is a common feature observed in most lung cancers. Gefitinib and erlotinib are commonly available therapeutic drugs which act as specific inhibitors for the tyrosine kinase domain of EGFR and associated with EGFR mutations in exons 18-21. However the prevalence of mutation varies among ethnicity, grade, age and gender. This is the first report on the prevalence of EGFR mutation in non-small cell lung cancer patients using DNA obtained from samples such as biopsy/cytology/pleural fluid and Fine Needle Aspiration (FNA), across India. We have screened for 29 somatic mutations which span exons 18, 19, 20 and 21 of EGFR gene using Scorpion probe based ARMS-PCR technique. DNA from 220 NSCLC tissue samples were analyzed for EGFR mutations and mutations were detected in 51.8% of the study population. Among the mutant positive cases, the deletions in exon 19 (52%) and a missense mutation L858R in exon 21 (26%) were most predominant. There was a significant increase in overall mutations (p=0.01) as a function of age, mutation in exons 19 and 21 together (p=0.003), mutations in exons 18, 19 and 21 (p=0.04) and mutations in exons 18 and 19 (p=0.03) in females. Mutations did not seem to significantly correlate metastases or disease progression. Mutations in exons [19] and 21 together were significant in non-smokers compared to smokers (p=0.01) using Mann-Whitney tests. The study suggests high prevalence of EGFR positivity in NSCLC in Indian sub-population and provides opportunities for targeted therapies for this group. |
| Databáze: | OpenAIRE |
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