Role of CDKN2A/p16 expression in the prognostication of oral squamous cell carcinoma

Publication date: October 2017
Source:Oral Oncology, Volume 73
Author(s): Swati Shree Padhi, Souvick Roy, Madhabananda Kar, Arka Saha, Shomereeta Roy, Amit Adhya, Manas Baisakh, Birendranath Banerjee
ObjectiveCDKN2A/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 methodSystematic 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.ResultSystematic 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 asa 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.ConclusionCDKN2A/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.



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