Amplification of EGFR and cyclin D1 genes associated with human papillomavirus infection in oral squamous cell carcinoma.
Jureeporn ChuerduangphuiChamsai PientongNatcha PatarapadungkitApinya ChotiyanoPatravoot VatanasaptBunkerd KongyingyoesSupannee PromthetPiyawut SwangphonSureewan BumrungthaiCharinya PimsonTipaya EkalaksanananPublished in: Medical oncology (Northwood, London, England) (2017)
Human papillomavirus (HPV) infection is associated with several genetic alterations including oncogene amplification, leading to increased aggression of tumors. Recently, a relationship between HPV infection and oncogene amplification has been reported, but this finding remains controversial. This study therefore investigated relationships between HPV infection and amplification of genes in the epidermal growth factor receptor (EGFR) signaling cascade in oral squamous cell carcinoma (OSCC). Extracted DNA from 142 formalin-fixed paraffin-embedded (FFPE) OSCC tissues was performed to investigate the copy number of EGFR, KRAS, c-myc and cyclin D1 genes using real-time polymerase chain reaction (RT-PCR) and compared with calibrators. A tissue microarray of OSCC tissues was used for detection of c-Myc expression and HPV infection by immunohistochemistry and HPV E6/E7 RNA in situ hybridization, respectively. HPV infection was also investigated using PCR and RT-PCR. Of the 142 OSCC samples, 81 (57%) were HPV-infected cases. The most frequently amplified gene was c-myc (55.6%), followed by cyclin D1 (26.1%), EGFR (23.9%) and KRAS (19.7%). Amplification of c-myc was significantly associated with levels of its protein product. EGFR amplification was also significantly associated with amplification of genes in the signaling cascade: KRAS (50.0%), c-myc (34.2%) and cyclin D1 (46.0%). Interestingly, HPV infection was significantly associated with amplification of both EGFR (76.5%) and cyclin D1 (73.0%). Only cyclin D1 amplification was significantly associated with severity of OSCC histopathology. HPV infection may play an important synergistic role in amplification of genes in the EGFR signaling cascade, leading to increased aggression in oral malignancies.
Keyphrases
- epidermal growth factor receptor
- nucleic acid
- small cell lung cancer
- tyrosine kinase
- high grade
- copy number
- genome wide
- cell cycle
- label free
- advanced non small cell lung cancer
- cervical cancer screening
- poor prognosis
- genome wide identification
- dna methylation
- high resolution
- drug delivery
- transcription factor
- small molecule
- long non coding rna
- cancer therapy