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Open Access Research article

LINE-1 and Alu hypomethylation in mucoepidermoid carcinoma

Porntipa Sirivanichsuntorn1, Somboon Keelawat2, Kittipong Danuthai3, Apiwat Mutirangura4, Keskanya Subbalekha1* and Nakarin Kitkumthorn5*

Author affiliations

1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand

2 Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand

3 Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand

4 Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand

5 Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand

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Citation and License

BMC Clinical Pathology 2013, 13:10  doi:10.1186/1472-6890-13-10

Published: 19 March 2013

Abstract

Background

Mucoepidermoid carcinoma (MEC) can be classified into low-, intermediate-, and high-grade tumors based on its histological features. MEC is mainly composed of three cell types (squamous or epidermoid, mucous and intermediate cells), which correlates with the histological grade and reflects its clinical behavior. Most cancers exhibit reduced methylation of repetitive sequences such as Long INterspersed Element-1 (LINE-1) and Alu elements. However, to date very little information is available on the LINE-1 and Alu methylation status in MEC. The aim of this study was to investigate LINE-1 and Alu element methylation in MEC and compare if key differences in the methylation status exist between the three different cell types, and adjacent normal salivary gland cells, to see if this may reflect the histological grade.

Methods

LINE-1 and Alu element methylation of 24 MEC, and 14 normal salivary gland tissues were compared using Combine Bisulfite Restriction Analysis (COBRA). Furthermore, the three different cell types from MEC samples were isolated for enrichment by laser capture microdissection (LCM), essentially to see if COBRA was likely to increase the predictive value of LINE-1 and Alu element methylation.

Results

LINE-1 and Alu element methylation levels were significantly different (p<0.001) between the cell types, and showed a stepwise decrease from the adjacent normal salivary gland to the intermediate, mucous and squamous cells. The reduced methylation levels of LINE-1 were correlated with a poorer histological grade. In addition, MEC tissue showed a significantly lower level of LINE-1 and Alu element methylation overall compared to normal salivary gland tissue (p<0.001).

Conclusions

Our findings suggest that LINE-1 methylation differed among histological grade mucoepidermoid carcinoma. Hence, this epigenetic event may hold value for MEC diagnosis and prognostic prediction.

Keywords:
Mucoepidermoid carcinoma (MEC); Methylation; Long INterspersed Element-1s (LINE-1s); Alu element; Laser capture microdissection