Nonrandom, widespread promoter methylation of tumor suppressor genes is a common mechanism of gene inactivation during tumorigenesis. We examined the methylation status of two distinct regions of the MLH1 promoter (proximal and distal to the transcription start site) and the MLH1 gene expression by methylation-specific PCR and immunohistochemistry. A total of 72 colorectal tumors, both with (n = 51, 22 affected by hereditary nonpolyposis colorectal cancer, HNPCC, defined according to the international clinical criteria and 29 sporadic cases) and without microsatellite instability (MSI) (n = 21) were studied. Methylation was present in at least one of the two promoter regions in 86% of the sporadic MSI cases, in 33% of the cases lacking MSI, and in 23% of the HNPCC tumors. In the HNPCC cases with a known MLH1 mutation (n = 10) none of the two promoter regions was methylated. Hypermethylation in both MLH1 promoter regions was seen in 45% of the MSI sporadic cases vs. 5% of the MSI-negative cases and 0% of the HNPCC cases. The overall concordance between the two promoter regions regarding methylation status was good (P = 0.009), but no significant correlation between methylation and suppression of the MLH1 immunohistochemical expression was found. Our data confirm that mutation and hypermethylation are mutually exclusive mechanisms in inducing mismatch repair deficiency and support the hypothesis of methylation as a process evenly distributed along the different regions of the promoter.
|Data di pubblicazione:||2001|
|Titolo:||Methylation pattern of different regions of the MLH1 promoter and silencing of gene expression in hereditary and sporadic colorectal cancer.|
|Autore/i:||Menigatti M;Di Gregorio C;Borghi F;Sala E;Scarselli A;Pedroni M;Foroni M;Benatti P;Roncucci L;Ponz de Leon M;Percesepe A|
|Digital Object Identifier (DOI):||10.1002/gcc.1154|
|Codice identificativo ISI:||WOS:000169722100006|
|Codice identificativo Scopus:||2-s2.0-0034946935|
|Codice identificativo Pubmed:||11433526|
|Citazione:||Methylation pattern of different regions of the MLH1 promoter and silencing of gene expression in hereditary and sporadic colorectal cancer / Menigatti M;Di Gregorio C;Borghi F;Sala E;Scarselli A;Pedroni M;Foroni M;Benatti P;Roncucci L;Ponz de Leon M;Percesepe A. - In: GENES, CHROMOSOMES & CANCER. - ISSN 1045-2257. - STAMPA. - 31(2001), pp. 357-361.|
|Tipologia||Articolo su rivista|
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