LINE-1 and Alu Methylation Patterns in Lymph Node Metastases of Head and Neck Cancers

Kitkumthorn, Nakarin; Keelawat, Somboon; Rattanatanyong, Prakasit; Mutirangura, Apiwat

doi:10.7314/apjcp.2012.13.9.4469

Cited by 29 publications

(32 citation statements)

References 33 publications

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“…We characterized the methylation status of the repetitive sequences in clinical samples of MEC, and our results clearly show that LINE-1 hypomethylation is in concordant with a poorer histological grade. The COBRA technique represents an excellent approach for detecting the methylation status [41,47], and using for example COBRALINE-1 and COBRAAlu, both are effective in detecting genome-wide methylation status of LINE-1s and Alu elements, respectively, in genomic DNA [48]. In our study, we used a modified method for COBRALINE-1 and COBRAAlu assessing the methylation status, as shown in Figure 1.…”

Section: Discussionmentioning

confidence: 99%

LINE-1 and Alu hypomethylation in mucoepidermoid carcinoma

et al. 2013

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BackgroundMucoepidermoid 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.MethodsLINE-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.ResultsLINE-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).ConclusionsOur 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.

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Section: Discussionmentioning

confidence: 99%

LINE-1 and Alu hypomethylation in mucoepidermoid carcinoma

et al. 2013

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“…Methylation levels of Alu elements and long interspersed element-1 s (LINE-1 s) have been evaluated in cancer, autoimmune disease, and aging. Alu and LINE-1 hypomethylation are commonly reported in cancer [2]–[4]. (Kitkumthorn N, 2011 #2) Hypomethylation of LINE-1 but not Alu has been reported in systemic lupus erythematosus patients [5].…”

Section: Introductionmentioning

confidence: 99%

Hypomethylation of Alu Elements in Post-Menopausal Women with Osteoporosis

et al. 2013

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A decrease in genomic methylation commonly occurs in aging cells; however, whether this epigenetic modification leads to age-related phenotypes has not been evaluated. Alu elements are the major interspersed repetitive DNA elements in humans that lose DNA methylation in aging individuals. Alu demethylation in blood cells starts at approximately 40 years of age, and the degree of Alu hypomethylation increases with age. Bone mass is lost with aging, particularly in menopausal women with lower body mass. Consequently, osteoporosis is commonly found in thin postmenopausal women. Here, we correlated the Alu methylation level of blood cells with bone density in 323 postmenopausal women. Alu hypomethylation was associated with advanced age and lower bone mass density, (P<0.05). The association between the Alu methylation level and bone mass was independent of age, body mass, and body fat, with an odds ratio [1] = 0.4316 (0.2087–0.8927). Individuals of the same age with osteopenia, osteoporosis, and a high body mass index have lower Alu methylation levels (P = 0.0005, 0.003, and ≤0.0001, respectively). Finally, when comparing individuals with the same age and body mass, Alu hypomethylation was observed in individuals with lower bone mass (P<0.0001). In conclusion, there are positive correlations between Alu hypomethylation in blood cells and several age-related phenotypes in bone and body fat. Therefore, reduced global methylation may play a role in the systemic senescence process. Further evaluation of Alu hypomethylation may clarify the epigenetic regulation of osteoporosis in post-menopausal women.

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“…LINE-1 hypomethylation is one of the most common epigenetic changes in cancer including HNSCC (Chalitchagorn et al, 2004;Smith, Mydlarz, Mithani, & Califano, 2007). Because circulating tumor DNA and cells can be in a mixture of sera or circulating cells, several studies reported LINE-1 methylation levels in circulating cells and sera to see its potential as tumor markers (Kitkumthorn, Keelawat, Rattanatanyong, & Mutirangura, 2012;Kitkumthorn, Tuangsintanakul, Rattanatanyong, Tiwawech, & Mutirangura, 2012;Pobsook, Subbalekha, Sannikorn, & Mutirangura, 2011;Schwarzenbach, Hoon, & Pantel, 2011;Widschwendter & Menon, 2006). However, our previous study suggested that LINE-1 methylation changes in circulation may include LINE-1 methylation changes in white blood cells (WBCs).…”

Section: Introductionmentioning

confidence: 99%

“…Using this technique, it is possible to determine the methylation patterns of the two CpG dinucleotides in the LINE-1 sequence (Pobsook et al, 2011). In addition to methylation levels, sqCOBRA-LINE-1 can distinguish methylation of LINE-1 alleles into four categories: methylation, unmethylation, and two forms of partial methylation (Kitkumthorn, Keelawat, et al, 2012;Kitkumthorn, Tuangsintanakul, et al, 2012). The COBRA technique has been proven to have equivalent precision similar to bisulfite pyrosequencing techniques (Jintaridth & Mutirangura, 2010;Rerkasem et al, 2015).…”

Section: Introductionmentioning

confidence: 99%