Mutation analysis of EGFR and its correlation with the HPV in Indian cervical cancer patients

Tumour Biol. 2016 Jul;37(7):9089-98. doi: 10.1007/s13277-016-4789-4. Epub 2016 Jan 14.

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.

Keywords: Correlation; EGFR; HPV16; Mutation.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • DNA Mutational Analysis / methods
  • ErbB Receptors / genetics*
  • Exons / genetics
  • Female
  • Gefitinib
  • HeLa Cells
  • Human papillomavirus 16 / pathogenicity*
  • Human papillomavirus 18 / pathogenicity*
  • Humans
  • India
  • Middle Aged
  • Mutation / drug effects
  • Mutation / genetics*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / virology
  • Protein Kinase Inhibitors / pharmacology
  • Quinazolines / pharmacology
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / virology*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib