Role of CDKN2A/p16 expression in the prognostication of oral squamous cell carcinoma. (October 2017)

• Record Type: Journal Article
• Authors: Padhi, Swati Shree; Roy, Souvick; Kar, Madhabananda; Saha, Arka; Roy, Shomereeta; Adhya, Amit; Baisakh, Manas; Banerjee, Birendranath
• Is Part Of: Oral oncology. Volume 73(2017)
• Page Start: 27
• Page End: 35
• Publication Date: 2017-10
• Subjects: Tumor suppressor gene -- Oral squamous cell carcinoma -- CDKN2A -- Recurrence -- Prognosis; OSCC oral squamous cell carcinoma -- NGS next generation sequencing -- FunDO functional disease ontology -- CGH comparative genome hybridization; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2017.07.030
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: 104 OSCC cases were screened for the expression of CDKN2A/p16. A deleterious loss of CDKN2A/p16 was confirmed by Array CGH and NGS. CDKN2A/p16 can be used a prognostic marker for the OSCC patients. 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 consistent downregulated expression of CDKN2A/p16 in the recurrent cases. The gene expression study confirmed 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 transformations occurring throughout disease progression.