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Assessment of MLH1 promoter methylation in relation to gene expression requires specific analysis

Oncogene volume 26, pages 7596–7600 (2007)Cite this article

Abstract

About 15% of colorectal cancers are called MSI because they demonstrate microsatellite instability. In most sporadic MSI cases, the DNA mismatch repair (MMR) defect is due to methylation of the MLH1 promoter. In hereditary MSI cases, it is the consequence of germline mutations of one of the MMR genes. We analysed the MLH1 promoter for methylation using the methylation-specific PCR technique. With a previously described and widely used primer set, a number of samples with an intact MMR system were found to have methylated MLH1 promoter, a finding normally associated with lack of MLH1 expression. Another primer set, specific for a more proximal region of the promoter, gave results that correlated more closely with loss of MLH1 expression. We then conducted a survey of the literature on the subject, and a total of 161 articles were examined. Although it was shown as early as 1999 that absence of MLH1 expression correlated with methylation of the proximal but not distal regions of the MLH1 promoter, 60% of published studies analysed nonspecific regions. Our findings suggest that these studies are likely to have wrongly estimated the association between methylation of the MLH1 gene and the lack of its protein expression.

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Acknowledgements

We thank Dr Barry Iacopetta for critical reading of the article. This work was partly supported by Association de la Recherche contre le Cancer, and an Interface grant from INSERM/Assistance Publique-Hôpitaux de Paris (AP-HP).

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Authors and Affiliations

  1. INSERM, U762, Paris, France

    E Capel, J-F Fléjou & R Hamelin

  2. Université Pierre et Marie Curie-Paris 6, IFR65, Paris, France

    E Capel, J-F Fléjou & R Hamelin

  3. AP-HP, Hôpital Saint-Antoine, Service d'Anatomo-Pathologie, Paris, France

    J-F Fléjou

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  1. E Capel
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  2. J-F Fléjou
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  3. R Hamelin
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Correspondence to R Hamelin.

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Capel, E., Fléjou, JF. & Hamelin, R. Assessment of MLH1 promoter methylation in relation to gene expression requires specific analysis. Oncogene 26, 7596–7600 (2007). https://doi.org/10.1038/sj.onc.1210581

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