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Query: UMLS:C1522102 (Melanoma)
 7,698 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microsatellite instability (MSI) is a distinct tumour phenotype that is associated with alterations of DNA mismatch repair and is being increasingly reported in a number of hereditary and sporadic tumours. Numerous reports have suggested that melanocytic neoplasms, including cutaneous melanomas, frequently demonstrate low frequency MSI, whilst a small number of tumours exhibit high frequency MSI. Furthermore, loss of expression of DNA mismatch repair proteins has been associated with progression from benign to malignant disease in melanocytic neoplasms, but the presence or absence of mismatch repair defects in uveal melanomas has yet to be determined. This study was designed to establish whether MSI is a feature of these ocular melanomas. To investigate the prevalence of MSI in uveal melanomas, 52 tumours were analysed by polymerase chain reaction amplification of a panel of microsatellite markers selected for their ability to detect tumours exhibiting defects in DNA mismatch repair mechanisms. MSI was rarely detected in the 52 uveal melanomas analysed. All tumours demonstrated stable microsatellites at five of the six microsatellite markers tested (BAT26, BAT40, APC, D2S123 and Mfd15CA). Only one tumour showed the presence of a single unstable allele at a tetranucleotide marker (MYCL1). These data suggest that high frequency MSI does not occur in these tumours, and that low frequency MSI, in contrast to cutaneous melanoma, is a rare event in malignant melanomas of the uveal tract.
Melanoma Res 2003 Oct
PMID:Instability of microsatellites is an infrequent event in uveal melanoma. 1451 84

Consorcial projects focused on 5 cancer types, breast-, colorectal-, head and neck- and pediatric cancers, and malignant melanoma. Breast cancer studies revealed unique splicing mechanisms concerning BRCA1. In sporadic breast cancers the involvement of DNA-repair genes was proved to be dependent on the histological type. Bone-metastatic tumors have been characterized by decreased NM23 and increased c-met and p53 expressions. C-erbB2 genotype of the primary tumor was not maintained frequently in bone metastases. Application of DNA-microarray and quantitative PCR technologies improved the prediction of therapeutic sensitivity of breast cancers. Colorectal cancer studies revealed regional inhomogenities (clusters) in various geographical regions of Hungary, which were distinct in the case of colonic and rectal cancers. To increase the sensitivity of fecal blood test of colorectal cancer screening, a new double-antibody test was developed and tested in a large cohort of patients. Genetic analysis revealed that hypermethylation is a significant factor in microsatellite instability which, and plays a role in silencing of APC and E-cadherin genes as well. The Hungarian pattern of TS polymorphism was also determined and was correlated not only with the efficacy of 5-FU treatment but with the progression of the disease as well. Population-based studies have been carried out in head and neck cancer patients (HNC) and smokers as well to reveal the genetic background of increasing tumor incidence. These studies revealed polymorphism in XRCC1/3 methylation enzyme gene which has preventive role. Other studies found frequent local immunosuppression in HNC patients. Studies indicated that the success of irradiation in this cancer type is dependent on the anti-vascular effects. Pediatric cancer studies determined the parameters of neuroblastoma screening based on VMA measurements. New splice variants of the WT1 gene involved in the monitoring of MRD of ALL patients was also described this year. We also obtained positive experimental data for the retinoic acid therapy of ALL. Melanoma studies extensively used DNA-microarray technology which identified 4 melanoma-specific and 2 melanoma progression-specific genes. In experimental human melanoma xenograft models we have identified 3 anti-metastatic agents: low molecular weight heparin, 2-methoxyestradiol and erythropoietin-alpha, where the later was characterized by specific effects on tumor vasculature.
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PMID:[Report of the National Oncology Research and Developement Consortium, 2003]. 1510

Malignant melanoma originates in melanocytes, the pigment-producing cells of the skin and eye, and is one of the most deadly human cancers with no effective cure for metastatic disease. Like many other cancers, melanoma has both environmental and genetic components. For more than 20 years, the melanoma genome has been subject to extensive scrutiny, which has led to the identification of several genes that contribute to melanoma genesis and progression. Three molecular pathways have been found to be nearly invariably dysregulated in melanocytic tumors, including the RAS-RAF-MEK-ERK pathway (through mutation of BRAF, NRAS or KIT), the p16 INK4A-CDK4-RB pathway (through mutation of INK4A or CDK4) and the ARF-p53 pathway (through mutation of ARF or TP53). Less frequently targeted pathways include the PI3K-AKT pathway (through mutation of NRAS, PTEN or PIK3CA) and the canonical Wnt signaling pathway (through mutation of CTNNB1 or APC). Beyond the specific and well-characterized genetic events leading to activation of proto-oncogenes or inactivation of tumor suppressor genes in these pathways, systematic high-resolution genomic analysis of melanoma specimens has revealed recurrent DNA copy number aberrations as well as perturbations of DNA methylation patterns. Melanoma provides one of the best examples of how genomic analysis can lead to a better understanding of tumor biology. We review current knowledge of the genes involved in the development of melanoma and the molecular pathways in which these genes operate.
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PMID:The genome and epigenome of malignant melanoma. 1804 49

The inactivation of tumor-related genes through the aberrant methylation of promoter CpG islands is thought to contribute to tumor initiation and progression. We therefore investigated promoter methylation events involved in cutaneous melanoma by screening 30 genes of interest for evidence of promoter hypermethylation, examining 20 melanoma cell lines and 40 freshly procured melanoma samples. Utilizing quantitative methylation-specific PCR, we identified five genes (SOCS1, SOCS2, RAR-beta 2, TNFSF10C, and TNFSF10D) with hypermethylation frequencies ranging from 50% to 80% in melanoma cell lines as well as freshly procured tissue samples. Eighteen genes (LOX, RASSF1A, WFDC1, TM, APC, TFPI2, TNFSF10A, CDKN2A, MGMT, TIMP3, ASC, TPM1, IRF8, CIITA-PIV, CDH1, SYK, HOXB13, and DAPK1) were methylated at lower frequencies (2-30%). Two genes (CDKN1B and PTEN), previously reported as methylated in melanoma, and five other genes (RECK, IRF7, PAWR, TNFSF10B, and Rb) were not methylated in the samples screened here. Daughter melanoma cell lines showed identical methylation patterns when compared with original samples from which they were derived, as did synchronous metastatic lesions from the same patient. We identified four genes (TNFSF10C, TNFSF10D, LOX, and TPM1) that have never before been identified as hypermethylated in melanoma, with an overall methylation frequency of 60, 80, 50, and 10%, respectively, hypothesizing that these genes may play an important role in melanoma progression.
Pigment Cell Melanoma Res 2008 Oct
PMID:Identification of novel epigenetically modified genes in human melanoma via promoter methylation gene profiling. 1862 28

Melanoma is the main serious skin cancer, due to its high lethality. This study aimed to make projections and analyze melanoma mortality trends in Brazil. Mortality Information System data were utilized for the period 1998-2012, which were projected until 2032, using the age-period-cohort model, with software R. The analysis of trends was made by Joinpoint regression, with 95% confidence interval, estimating the annual percentage change. It was revealed higher amounts of deaths in men for all regions. Brazilian trends presented reductions in men (APC = -0.4; CI95% = -0.6; -0.1; p < 0.01) and in women (APC = -0.8; CI95% = -0.9; -0.7; p < 0.01). The Midwest region presented increases for both sexes, while the Southeast region presented reducing trends for both sexes. In the North, there was stability for men and increases followed by stability in women, while the South presented reductions in men and stability in women; finally, the Northeast revealed one joinpoint per sex, with an increase followed by stability in men, and stability followed by reducing trends in women. The highest rates of the country were found in the South and Southeast regions, however, with reducing trends throughout time. Higher mortality trends in men were associated with later diagnoses in this group.
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PMID:Melanoma mortality in Brazil: trends and projections (1998-2032). 3106 56