CLINICAL IMPLICATIONS OF p53 ALTERATIONS IN ORAL CANCER PROGRESSION: A REVIEW FROM INDIA

Abstract

p53 plays a central role in prevention of normal cell from the development of the malignant phenotype. Somatic alterations (mutations, loss of heterozygosity, deletions) in p53 are a hallmark of most human cancers and cause defects in normal p53 function. However, in the tumors harboring wild-type p53, there are alterations in the regulation of the p53. Thus, understanding why p53 is unable to perform its role as a tumor suppressor in these wild-type tumors is very crucial. Germ-line polymorphisms in p53 are also anticipated to cause measurable disturbance in p53 function. Over-expression as well as polymorphic variants of MDM2 might have effects on cancer development. In addition, degradation of p53 by E6 protein of high risk human papillomavirus is also suggested as one of the mechanisms which attenuate p53 responses in oral carcinogenesis. p53 has also been demonstrated to mediate cellular responses upon various DNA damaging cancer therapies, importantly, apoptosis. These responses have been implicated in an individual’s ability to respond to these cancer therapies. Thus, exploring mechanisms by which normal function of p53 is affected in the comprehensive way in oral cancer might aid in the identification of tumor characteristics, prognosis and thus in the development of a new approach to treat the oral cancer.

A review on the most important viruses in oral cavity cancers

“…P53 has an important role in preventing the formation of malignant cells from normal cells. In a study by Patel et al [54], destruction of p53 by E6 in high-risk HPVs was considered as a possible mechanism for the observed low level of p53 in oral cancers. Similarly, Walline and Pinatti showed that viral integration with micro-RNAs alter the expression of regulatory molecules and may facilitate oncogenesis [55].…”

Genetic mutations of exon 4 at TP53 gene in oral cavity cancers

“…The latter binds and promotes the degradation of the TP53 tumor suppressor gene product [7]. This gene is widely used in the study of cancers as it is commonly mutated in human cancers and in about 50% of malignant tumors [1,8]. Several mechanisms lead to the alteration of the P53 protein response, but somatic mutations in the gene are one of the most universal mechanisms during oral carcinogenesis.…”

“…Its prognostic value in OCC has long been debated. Conflicting results have been published on the presence or absence of mutations in this gene, with variations in their frequencies across OCCs [8].…”

Association of the TP53 Arg72Pro Polymorphism with Oral Squamous Cell Carcinoma: A Meta-Analysis

“…More than 50% of cancers in humans express a mutation in this gene [3][4][5]. The encoded protein mediates in the prevention of neoplastic transformation by repairing DNA damages after replication, or by inducing apoptosis in case DNA damages couldn't be repaired [6].…”