Search results for " like the most part of tumors. This result raises the possibility that susceptibility to lymphomas is related to abnormal DNA methylation levels and suggests the opportunity to evaluate the DNA methylation status in RA patient"

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Metilazione del DNA in artrite reumatoide

2005

Lo stato di metilazione del DNA genomico e del gene PTHrP è stato valutato con tecniche molecolari e citogenetiche in artrite reumatoide (AR), patologia autoimmune caratterizzata anche da alta incidenza di linfomi e da ipercalcemia per overespressione del gene PTHrP. La metilazione del DNA, infatti, ha un ruolo critico nello sviluppo delle malattie neoplastiche; il gene PTHrP avendo tre promotori uno dei quali contiene un’isola CpG è un buon candidato per la deregolazione da alterato pattern di metilazione locale. Le indagini sulla metilazione genomica, condotte su DNA estratto da sangue periferico di pazienti e di donatori e amplificato in reazioni di Methylation-Sensitive Arbitrarily Prim…

Settore BIO/18 - Geneticainstead chromosomes of controls were almost uniformly decorated by brilliant grains. Studies on methylation of PTHrP gene promoter 2 performed on five CpG island internal sites using the Methylation-Sensitive Restriction Endonuclease Multiplex (MSREM)-PCR showed that one of the sites nearest the trascription starting point is heavy methylated in a significantly high number of RA patients. Thus RA seems to be characterized by genomewide hypomethylation associated with local hypermethylation like the most part of tumors. This result raises the possibility that susceptibility to lymphomas is related to abnormal DNA methylation levels and suggests the opportunity to evaluate the DNA methylation status in RA patientin fact the demethylating therapies together with diet and life style can act towards an increase of tumor risk. Future studies using a larger number of subjects could confirm these findings.Rheumatoid Arthritis (RA) is a chronic multisystem inflammatory disease characterized by high recurrence of lymphomas as well as hypercalcemia due to PTHrP overexpression. Because of DNA methylation plays a critical role in development of neoplasias we determined in RA patients the global DNA methylation status and local methylation pattern of the CpG island of one of the three promoters of PTHrP gene utilizing molecular and cytogenetic techniques. Investigations performed on DNA from peripheral blood of patients and donors amplified by Methylation-Sensitive Arbitrarily Primed (MeS-AP)-PCR indicated that RA is strongly associated with global DNA hypomethylation. Similarly chromosomal DNA methylation pattern analysis by indirect immunofluorescence technique with anti 5-methylcitosine antibody showed all peripheral lymphocyte metaphases from RA patients with chromosomes weakly fluorescent without discrete grain
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