The Harvey and Kirsten strains of murine sarcoma virus encode enzymatically and serologically related p21 src proteins which are required for virally mediated cellular transformation. The genes in each virus encoding p21 show such extensive divergence from each other that cloned probes from these genes detect distinct sets of cellular genes in the DNA from several vertebrate species. These data suggest that cellular p21 sarc genes constitute a divergent family of vertebrate genes that can regulate the growth of cells.

The mitochondrial inner membrane contains a large protein complex that functions in inner membrane organization and formation of membrane contact sites. The complex was variably named the mitochondrial contact site complex, mitochondrial inner membrane organizing system, mitochondrial organizing structure, or Mitofilin/Fcj1 complex. To facilitate future studies, we propose to unify the nomenclature and term the complex “mitochondrial contact site and cristae organizing system” and its subunits Mic10 to Mic60.

Aberrant promoter hypermethylation of tumor-associated genes leading to their inactivation is a common event in many cancer types. Using a sensitive restriction-multiplex PCR method, we studied the promoter hypermethylation profile of the p16, p15, hMLH1, MGMT and E-cad genes in oral squamous cell carcinoma (OSCC) of Indians. We analyzed a total of 51 samples for the p15 tumor-suppressor gene and 99 samples for each of the remaining genes. Our studies indicate an incidence of promoter hypermethylation of 23% each for p16 and p15, 8% for hMLH1, 41% for MGMT and 35% for E-cad. We observed aberrant hypermethylation of the promoter region of at least 1 of these genes in 74.5% of cases (n ‫؍‬ 51) for which all the 5 genes were studied. Abnormal methylation was detected in tumors irrespective of stage and location in the oral cavity, whereas no abnormal methylation was detectable in normal oral squamous tissues obtained from 25 OSCC patients. Oral squamous cell carcinoma (OSCC) is one of the most widely prevalent cancer types in developing countries, including India, and is associated with tobacco and alcohol abuse. 1 Although recent research has given deeper insight into the etiology of the disease, its occurrence as a potentially fatal disease continues unabated. It is therefore essential to identify and develop newer risk markers for diagnosis and therapy of OSCC.Methylation profiling of promoter regions is essential for understanding the regulation of imprinted genes, X-chromosome inactivation and the role of various tumor-suppressor genes in the genesis of different types of cancer. 2,3 Methylation profiling of tumor-suppressor genes is a potentially powerful diagnostic tool for early detection of various types of cancer. 3-5 Assessment of methylation inactivation is important in assigning functional roles of genes and may have implications in the function of other interacting proteins. 3,6 Inactivation of several tumor-associated genes, especially tumor-suppressor genes, has been attributed to aberrant hypermethylation of their promoter regions. 2,3,6 We included in our study 5 tumor-suppressor genes: p16, a CDK inhibitor involved in regulation of the cell cycle by the cyclin D-Rb pathway, control of which is lost in virtually all tumor types; 7 p15, another CDK inhibitor involved in cell-cycle regulation; 8 hMLH1, the human homolog of bacterial MutL, involved in mismatch repair; 9 MGMT, the gene involved in repair of methylated guanosine residues formed due to alkylated carcinogens; and E-cadherin, involved in homotypic epithelial cell-cell adhesion. 10 All of these genes are known to be inactivated by methylation in various cancers. 3,11 Methylation profiling of CpG sites originally involved digestion of sample DNA using a methylation-sensitive restriction enzyme followed by Southern hybridization 7,12 or PCR using primers flanking the restriction site. [13][14][15] Using these assays, methylation patterns could not be determined from very small amounts of DNA and the occurrence of false-negatives due to degra...

The transforming protein of Kirsten murine sarcoma virus (Ki-MuSV) is a virally encoded 21-kilodalton protein called p21 kis. The sequences encoding p21 kis were genetically localized to a 1.3-kilobase segment near the 5' end of the viral genome by assaying the capacity of a series of defined deletion mutants of molecularly cloned Ki-MuSV DNA to induce focal transformation of mouse cells. Nucleotide sequencing of a portion of this region has led to the identification of an open reading frame of 567 nucleotides coding for p21 kis protein.

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