Role of CDKN2A/p16 expression in the prognostication of oral squamous cell carcinoma Swati Shree Padhi a,1 , Souvick Roy a,1 , Madhabananda Kar b , Arka Saha a , Shomereeta Roy a , Amit Adhya c , Manas Baisakh d , Birendranath Banerjee a,⇑ a Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024, India b Department of Surgical Oncology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha 751016, India c Department of Pathology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, Odisha 751024, India d Department of Pathology, Apollo Hospitals, Bhubaneswar, Odisha 751004, India article info Article history: Received 6 March 2017 Received in revised form 11 July 2017 Accepted 28 July 2017 Keywords: Tumor suppressor gene Oral squamous cell carcinoma CDKN2A Recurrence Prognosis abstract Objective: CDKN2A/p16 is a known tumor suppressor gene with a homologous deletion in Oral Squamous cell carcinoma. CDKN2A/p16 is found to be inactivated in a broad spectrum of solid tumors and in more than 80% of OSCC. Molecular alteration of CDKN2A/p16 in progression of OSCC can pose an important tool for the prognosis of squamous cell carcinoma. Material and method: Systematic network analysis was carried out to obtain involvement of CDKN2A/p16 in oral cancer by polysearch and FunDO. In the present study we have screened 104 OSCC patients from eastern region of India for CDKN2A/p16 expression in recurrent and non-recurrent OSCC. The observation was validated by Comparative Genomic Hybridisation and Next generation sequencing in recurrent cases. Result: Systematic analysis revealed direct involvement of CDKN2A/p16 in oral cancer. There was a con- sistent downregulated expression of CDKN2A/p16 in the recurrent cases. The gene expression study con- firmed a >5-fold downregulation of CDKN2A/p16 in recurrent tumors as compared to non-recurrent ones. Array CGH analysis revealed a copy number deletion in the recurrent case. Furthermore, next generation sequencing validated deletion of CDKN2A/p16 and reported it as a common variant with a nonsense mutation having stop /loss of function of the gene in recurrent cases. Recurrent cases with deleted CDKN2A/p16 expression had poor prognosis and low survival rate. Conclusion: CDKN2A/p16 frequently alters in oral cancer progression with a deletion/loss of function in the recurrent cases displaying its role in aiding several molecular events for the malignant transforma- tions occurring throughout disease progression. Ó 2017 Elsevier Ltd. All rights reserved. Introduction Rate of recurrence of oral squamous cell carcinoma (OSCC) has been on a rise, ranging from 30% to 47% in the last decades, despite numerous progresses in chemotherapy, radiotherapy and targeted therapy [1]. Recurrence is a major prognostic factor in the patients with OSCC [2]. An aggressive tumor with local invasion and metas- tasis leads to poor prognosis and recurrence [2]. Telomere dysfunc- tion has been an important hallmark in progression of the squamous cell carcinoma from severe dysplasia to higher grade malignant tumor [3,4]. Alteration of various repair factors occurs due to severe genome instability and associated mutational events during progression of disease resulting in their loss of function [5,6]. Thus need for prognostic markers may serve as indicative tools for pathological investigations in regular procedure of early diagnosis and treatment. Onset of tumorigenesis and progression of the infiltrating front involves massive DNA damage and repair [7,8]. The process is also aided by continuous telomere dysfunction with dedifferentiation [4,8]. The growth advantage of aggressive tumor cells is achieved by dysregulation of various growth promoting genes [4,9,10]. Wnt/b-catenin pathway is reported to be dysregulated in various solid tumors [9–11]. These pathways along with involvement of http://dx.doi.org/10.1016/j.oraloncology.2017.07.030 1368-8375/Ó 2017 Elsevier Ltd. All rights reserved. Abbreviations: OSCC, oral squamous cell carcinoma; NGS, next generation sequencing; FunDO, functional disease ontology; CGH, comparative genome hybridization. ⇑ Corresponding author at: KIIT School of Biotechnology, KIIT University, Bhubaneshwar 751024, Odisha, India. E-mail address: bnbanerjee@kiitbiotech.ac.in (B. Banerjee). 1 Authors contributed equally. Oral Oncology 73 (2017) 27–35 Contents lists available at ScienceDirect Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology