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Viral Oncogenes (viral + oncogene)
Selected AbstractsStructural variability of the carboxy-terminus of Epstein,Barr virus encoded latent membrane protein 1 gene in Hodgkin's lymphomasJOURNAL OF MEDICAL VIROLOGY, Issue 11 2007Deisy M. Guiretti Abstract Epstein,Barr virus (EBV) is implicated in the pathogenesis of several lymphoid and epithelial neoplasms. Latent membrane protein 1 (LMP1) is the major viral oncogene and it is controversial whether tumor LMP1 variants reflect their geographical predominance or are associated with enhanced oncogenic properties. This study aimed to analyze LMP1 molecular variability of 62 EBV+ Hodgkin's lymphomas and 22 non-neoplastic controls from Brazil and Argentina. EBV association was characterized by EBER-ISH, LMP1 immunohistochemistry and PCR assays for EBNA2 and 3C (typing), LMP1 30 bp deletion (del30) and number of 33 bp tandem repeats. LMP1 C-terminal sequencing was performed in 42 cases. EBV1 was the predominant strain in both geographical Hodgkin's lymphoma groups (average 82%). A higher frequency of del30 variant was observed in lymphomas (41/63) than in non-neoplastic controls (6/22) (OR 4.97, CI 95% 1.53,16.79; P,=,0.005, ,2 test). A large number (5,7) of 33 bp repeat units was characteristic of del30 LMP1 variants (P,<,0.0001, Fisher's exact test). Sequence analysis showed a similar mutation spectrum to that described worldwide but none of the current classification schemes could be applied completely. A distinct structural pattern was observed in del30 variants, characterized by a large number of 33 bp repeat units and the presence of a 15 bp insertion encoding the JAK3 Box-1a motif (3/15 wt vs. 16/20 del30; P,=,0.001, ,2 test). The results suggest a pathogenic role for LMP1 del30 variants in Hodgkin's lymphoma from South America and point to particular virus-host molecular mechanisms, such as genomic instability in LMP1 carboxy-terminus, leading to enhanced production and selection of these deletion variants. J. Med. Virol. 79:1722,1730, 2007. © 2007 Wiley-Liss, Inc. [source] Analysis of genetic stability at the EP300 and CREBBP loci in a panel of cancer cell lines,GENES, CHROMOSOMES AND CANCER, Issue 2 2003Guy W. Tillinghast EP300 (p300) and CREBBP (CBP) are highly related transcriptional co-activators possessing histone acetyltransferase activity. These proteins have been implicated in coordinating numerous transcriptional responses that are important in the processes of proliferation and differentiation. A role for EP300 and CREBBP as tumor suppressors in cancer has been suggested by the fact that they are targeted by viral oncogenes; there is an increased incidence of hematologic malignancies in mice monoallelic for CREBBP; and loss, albeit at a low frequency, of both EP300 alleles in epithelial cancers has been observed. Because the level of EP300/CREBBP appears to have a critical effect on integrating certain transcriptional processes, we sought to determine whether a loss in the combined gene dosage of EP300 and CREBBP might play a role in cancer. Accordingly, we screened a panel of 103 cell lines for loss of heterozygosity and found 35 and 51% LOH for the CREBBP and EP300 loci, respectively. Concordant loss of CREBBP and EP300 was not associated with mutations in important regions of the remaining EP300 or CREBBP genes. In addition, there did not appear to be a statistically significant selection in cancer cells, stratified by various criteria, for the concordant loss of EP300 and CREBBP. We conclude that EP300 and CREBBP rarely act as classical tumor suppressors in human cancer. Published 2003 Wiley-Liss, Inc. [source] Antibodies against human papillomavirus (HPV) type 16 and 18 E2, E6 and E7 proteins in sera: Correlation with presence of papillomavirus DNAJOURNAL OF MEDICAL VIROLOGY, Issue 4 2001Ricardo Rosales Abstract Human papillomavirus (HPV) infection is associated with cervical cancer. The E2 and E1 papillomavirus proteins are expressed at the early stage of infection and regulate DNA replication. The E2 protein activates and represses transcription from different HPVs promoters. At some stage when viral DNA gets integrated into the cellular genome, the E2 gene is disrupted or inactivated. This event leads to a derepression of the E6 and E7 viral oncogenes. These viral proteins are required normally for the maintenance of the malignant phenotype. Therefore, the E2, E6, and E7 proteins are present in all patients infected by papillomavirus. In this study, the association of antibody levels against E2, E6, and E7 proteins of HPV types 16, 18, and 6 was determined in relation to the presence of HPV DNA at the initial stages of HPV infection. Serum samples from 172 women with HPV infection, determined by Papanicolau (Pap) smears and colposcopy, were tested. Elevated antibody titers against E2 protein from the HPV 6 and HPV 16 were detected in 46.42 and 66.96% of the patients, respectively. Antibodies against the E7 and E6 proteins of HPV 16 were found in 51.78 and 36.60% of the patients, respectively. Antibodies against the E6 and E7 proteins of HPV 18 were 35 and 45%, respectively. A statistical difference was found for antibody titers against the E2, E6, and E7 proteins between patients with papillomavirus DNA and controls cases who had no cytological abnormalities and no HPV DNA. Sera titers were 1/500 for patients HPV positive and 1/50 for control individuals. Antibodies titers against E6 and E7 proteins were also examined in patients at 6 and 24 months after cryosurgery. In these patients, a slight decrease in the antibody level against the E2, E6, and E7 proteins was found. No correlation was found between age and number of sexual partners, with serum positivity to the E2, E6, and E7 papillomavirus proteins. These data suggest that antibodies against the E2, E6, and E7 proteins are good candidates for use as markers for monitoring cervical HPV infections. J. Med. Virol. 65:736,744, 2001. © 2001 Wiley-Liss, Inc. [source] Positive selection in the evolution of cancerBIOLOGICAL REVIEWS, Issue 3 2006Bernard J. Grespi ABSTRACT We hypothesize that forms of antagonistic coevolution have forged strong links between positive selection at the molecular level and increased cancer risk. By this hypothesis, evolutionary conflict between males and females, mothers and foetuses, hosts and parasites, and other parties with divergent fitness interests has led to rapid evolution of genetic systems involved in control over fertilization and cellular resources. The genes involved in such systems promote cancer risk as a secondary effect of their roles in antagonistic coevolution, which generates evolutionary disequilibrium and maladaptation. Evidence from two sources: (1) studies on specific genes, including SPANX cancer/testis antigen genes, several Y-linked genes, the pem homebox gene, centromeric histone genes, the breast cancer gene BRCA1, the angiogenesis gene ANG, cadherin genes, cytochrome P450 genes, and viral oncogenes; and (2) large-scale database studies of selection on different functional categories of genes, supports our hypothesis. These results have important implications for understanding the evolutionary underpinnings of cancer and the dynamics of antagonistically-coevolving molecular systems. [source] | ||||||||||