Molecular characterisation in tongue squamous cell carcinoma reveals key variants potentially linked to clinical outcomes

Article type: Research Article

Authors: Alsofyani, Abeer A.^a | Dallol, Ashraf^{b; c; *} | Farraj, Suha A.^{d; j} | Alsiary, Rawiah A.^a | Samkari, Alaa^e | Alhaj-Hussain, Baraa T.^e | Khan, Jalaluddin Azam^f | Al-Maghrabi, Jaudah^g | Al-Khayyat, Shadi S.^h | Alkhatabi, Heba^{b; c} | Elaimi, Aisha^{b; c} | Buhmeida, Abdelbaset^{b; c} | Johargy, Ayman Khalidⁱ | Abuzenadah, Adel M.^{b; c} | Azhar, Esam I.^{c; d; *} | Al-Qahtani, Mohammed H.^{b; c}

Affiliations: [a] King Abdullah International Medical Research Center and King Saudbin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, Saudi Arabia | [b] Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia | [c] Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia | [d] Special Infectious Agent Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia | [e] Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, Saudi Arabia | [f] Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia | [g] Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia | [h] Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia | [i] Medical Microbiology Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia | [j] Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

Correspondence: [*] Corresponding authors: Ashraf Dallol and Esam I. Azhar, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. E-mail: eazhar@kau.edu.sa.

Abstract: BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is a highly aggressive malignancy characterized by frequent recurrence, poor survival with relatively few therapeutic options due to the late diagnosis in many cases. OBJECTIVES: Understanding the molecular pathways underlying OTSCC tumourigenesis and the discovery of diagnostic and/or prognostic biomarkers. METHODS: We performed high-throughput mutational analysis of 44 OTSCC formalin-fixed paraffin-embedded (FFPE) cases using the Cancer Hotspots Panel (CHP) v2 on the Ion Torrent™platform. We determined the frequency of human papilloma virus (HPV) using PCR and Epstein bar virus (EBV) positivity using immunohistochemistry. As a control for EBV infection we screened matched non-tumourous tissues. RESULTS: Sequencing analysis identified missense, nonsense and frameshift mutations in TP53 (66%), PIK3CA (27%), CDKN2A (25%), EGFR (18%), and PTEN (14%). Interestingly, no significant associations were found between damaging mutations and clinicopathological data. A total of 10/44 of the OTSCC samples (23%) tested was positive for HPV18 DNA. OTSCC patients with positive HPV infection had worse overall survival compared to HPV-negative cases as determined by Kaplan-Meier survival (p= 0.023). Furthermore, EBNA1 expression showed a strong tumour-enriched expression pattern in 20 out of 21 samples (95%) in the epithelial compartments of the tissues analysed. CONCLUSIONS: Taken together, this study highlights that the two most common events in OTSCC are TP53 mutations and EBV positivity. Helping to understand the contribution of TP53 mutations and EBV infection events could serve as useful biomarkers for OTSCC.

Keywords: Tongue cancer, oral cancer, EBV, HPV, biomarkers

DOI: 10.3233/CBM-190897

Journal: Cancer Biomarkers, vol. 28, no. 2, pp. 213-220, 2020