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Cancer is caused by malfunctioning of genes that normally regulate cardinal processes including various nuclear functions, cell division and survival, cell surface to nucleus signaling cascades, etc. Cancer associated genes are often classified as oncogenes (OCGs) or tumor suppressor genes (TSGs) depending on whether they promote or suppress tumorigenesis, respectively. Such strict classification of cancer genes may however be an over-simplification. Several studies have highlighted a dual role for cancer genes, often impacting the same facet of tumorigenesis. Knowledge of a possible dichotomy of a cancer gene (particularly an OCG) is imperative when evaluating its possible utility as a therapeutic target. Though previous studies have extensively evaluated specific examples of cancer genes exhibiting a dual nature, efforts to unravel the molecular basis for such contrasting functions have been fewer. The current review is an attempt to delineate molecular events underlying the functional dichotomy of cancer genes at the DNA (mutations, gene fusions, etc.), RNA (alternative splicing, regulation through non-coding RNAs, etc.) and protein (isoforms, mis-localisation, post-translational modifications, proteolytic cleavage, etc.) levels. • Cancer genes may display a dual nature exhibiting oncogenic as well as tumor suppressor functions. • This dichotomy can manifest at DNA, RNA or protein level. • The dual nature significantly impacts development of targeted therapies. [ABSTRACT FROM AUTHOR]

Purpose: The tumor suppressor p53 is known to be inactivated frequently in various cancers. In addition, germline polymorphisms in TP53 are known to affect protein function and influence risk of developing different types of cancers. In this study, we analyzed the association of TP53 Pro72Arg polymorphism with squamous cell carcinoma of oral tongue (SCCOT) and esophagus (ESCC) in India. Methods: We assessed the distribution of TP53 Pro72Arg polymorphism in one hundred and fifteen and eighty two SCCOT and ESCC patients, respectively, with respect to one hundred and ten healthy controls from the same population. In addition, we analyzed association of the polymorphism with several clinico-pathological and molecular parameters. Results: Pro72 allele was significantly enriched in SCCOT patients compared to the healthy control group but neither allele was enriched in ESCC. Interestingly, Pro72 allele was preferentially mutated in ESCC which was confirmed by analysis of samples heterozygous for Pro72Arg. Conclusions: Our study revealed the association of Pro72 allele with SCCOT suggesting the effect of this polymorphism on SCCOT risk. Preferential mutation of Pro72 allele exclusively in ESCC indicates the need for further studies to understand the tissue specific effect of p53 polymorphism. [ABSTRACT FROM AUTHOR]