Open Access Open Badges Research article

Correlation of MLH1 and MGMT expression and promoter methylation with genomic instability in patients with thyroid carcinoma

Juliana Carvalho Santos1, André Uchimura Bastos2, Janete Maria Cerutti2 and Marcelo Lima Ribeiro1*

Author Affiliations

1 Unidade Integrada de Farmacologia e Gastroenterologia, Universidade São Francisco, Av. São Francisco de Assis, 218. Jd. São José, Bragança Paulista, SP, Brazil

2 Laboratório as Bases Genéticas dos Tumores da Tiroide, Disciplina de Genética, Universidade Federal de São Paulo, São Paulo, SP, Brazil

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BMC Cancer 2013, 13:79  doi:10.1186/1471-2407-13-79

Published: 15 February 2013



Gene silencing of the repair genes MLH1 and MGMT was shown to be a mechanism underlying the development of microsatellite instability (MSI), a phenotype frequently associated with various human malignancies. Recently, aberrant methylation of MLH1, MGMT and MSI were shown to be associated with mutations in genes such as BRAF, RAS and IDH1 in colon and brain tumours. Little is known about the methylation status of MLH1 and MGMT in thyroid tumours and its association with MSI and mutational status.


In a series of 96 thyroid tumours whose mutational profiles of BRAF, IDH1 and NRAS mutations and RET/PTC were previously determined, we investigated MLH1 and MGMT expression and methylation status by qPCR and methylation-specific PCR after bisulphite treatment, respectively. MSI was determined by PCR using seven standard microsatellite markers.


Samples with point mutations (BRAF, IDH1 and NRAS) show a decrease in MLH1 expression when compared to negative samples. Additionally, malignant lesions show a higher MSI pattern than benign lesions. The MSI phenotype was also associated with down-regulation of MLH1.


The results of this study allow us to conclude that low expression of MLH1 is associated with BRAF V600E mutations, RET/PTC rearrangements and transitions (IDH1 and NRAS) in patients with thyroid carcinoma. In addition, a significant relationship between MSI status and histological subtypes was found.

Microsatellite instability; DNA methylation; DNA repair; Thyroid carcinoma