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Mutation analysis of EGFR and its correlation with the HPV in Indian cervical cancer patients
Rehana Qureshi1, Himanshu Arora2, Shilpi Biswas1
1Department of Biosciences, Genome Biology Laboratory, Jamia Millia Islamia, New Delhi, India.
Abstract:
Cervical cancer is a major cause of morbidity and mortality particularly in developing countries. Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is associated with increased sensitivity to tyrosine kinase inhibitors (TKIs). In this study, the presence of EGFR mutations in cervical cancer and its correlation with HPV were identified. EGFR mutations were found in 31 out of 95 patients (32.63 %). Results showed the presence of EGFR mutations in 5.263 % of patients in exon 19. In exon 20, mutations were predominant in 25.26 % patients. While in exon 21, 8.421 % of patients had mutations. HPV, which is associated with cervical cancer development, was found in 95.78 % (HPVL1), 92.63 % (HPV16), and 3.15 % (HPV18) of patients. No correlation was found between HPV16 and EGFR mutations (p = 0.0616). Overall, mutations like V742R, Q787Q, Q849H, E866E, T854A, L858R, E872Q, and E688Q were found. Next, impact of TKI inhibitor (gefitinib) was checked with respect to presence or absence of mutation considering Q787Q mutation in exon 20 (G/A genotype) which is present in 25.2 % patients. Mutated cervical cancer cell lines showed higher sensitivity to gefitinib. Overall, this study suggests the importance of mutations in EGFR gene and indicates their relevance with respect to TKIs treatment in Indian cervical cancer patients.
Insights
EGFR mutations are present in over 30% of cervical cancer patients, particularly in exon 20. These mutations suggest potential sensitivity to tyrosine kinase inhibitors (TKIs) like gefitinib, offering new treatment avenues for Indian cervical cancer patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Cervical cancer remains a significant global health issue, especially in developing nations.
- Somatic mutations in the epidermal growth factor receptor (EGFR) gene's tyrosine kinase domain are linked to enhanced sensitivity to tyrosine kinase inhibitors (TKIs).
Purpose of the Study:
- To investigate the prevalence of EGFR mutations in cervical cancer.
- To explore the correlation between EGFR mutations and Human Papillomavirus (HPV) infection.
- To assess the potential of TKIs in treating cervical cancer based on EGFR mutation status.
Main Methods:
- Analysis of EGFR gene mutations in 95 cervical cancer patients.
- Detection of HPV DNA (HPVL1, HPV16, HPV18) in patient samples.
- Evaluation of the sensitivity of mutated cervical cancer cell lines to the TKI gefitinib.
Main Results:
- EGFR mutations were detected in 32.63% of patients, with a high prevalence in exon 20 (25.26%).
- HPV was highly prevalent (95.78%), but no significant correlation was found between HPV16 and EGFR mutations (p=0.0616).
- Cervical cancer cell lines with specific EGFR mutations (e.g., Q787Q) exhibited increased sensitivity to gefitinib.
Conclusions:
- EGFR mutations are common in Indian cervical cancer patients and may predict response to TKIs.
- Targeted therapies involving TKIs could be a promising treatment strategy for a subset of cervical cancer patients.
- Further research is warranted to explore the clinical utility of EGFR mutation analysis in cervical cancer management.
