ABSTRACT
The molecular mechanisms that regulate stem cell pluripotency and differentiation has shown the crucial role that methylation plays in this process. DNA methylation has been shown to be important in the context of developmental pathways, and the role of histone methylation in establishment of the bivalent state of genes is equally important. Recent studies have shed light on the role of RNA methylation changes in stem cell biology. The dynamicity of these methylation changes not only regulates the effective maintenance of pluripotency or differentiation, but also provides an amenable platform for perturbation by cellular stress pathways that are inherent in immune responses such as inflammation or oncogenic programs involving cancer stem cells. We summarize the recent research on the role of methylation dynamics and how it is reset during differentiation and de-differentiation.
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 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. 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.
