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LINE-1 methylation patterns of different loci in normal and cancerous cells.

Phokaew C, Kowudtitham S, Subbalekha K, Shuangshoti S, Mutirangura A - Nucleic Acids Res. (2008)

Bottom Line: Therefore, the loss of genome-wide methylation in cancerous cells occurs as a generalized process.However, different LINE-1 loci showed different incidences of HNSCC hypomethylation, which is a lower methylation level than NOE.In conclusion, even though the global hypomethylation process that occurs in cancerous cells can generally deplete LINE-1 methylation levels, LINE-1 methylation can be influenced differentially depending on where the particular sequences are located in the genome.

View Article: PubMed Central - PubMed

Affiliation: Inter-Department Program of BioMedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.

ABSTRACT
This study evaluated methylation patterns of long interspersed nuclear element-1 (LINE-1) sequences from 17 loci in several cell types, including squamous cell cancer cell lines, normal oral epithelium (NOE), white blood cells and head and neck squamous cell cancers (HNSCC). Although sequences of each LINE-1 are homologous, LINE-1 methylation levels at each locus are different. Moreover, some loci demonstrate the different methylation levels between normal tissue types. Interestingly, in some chromosomal regions, wider ranges of LINE-1 methylation levels were observed. In cancerous cells, the methylation levels of most LINE-1 loci demonstrated a positive correlation with each other and with the genome-wide levels. Therefore, the loss of genome-wide methylation in cancerous cells occurs as a generalized process. However, different LINE-1 loci showed different incidences of HNSCC hypomethylation, which is a lower methylation level than NOE. Additionally, we report a closer direct association between two LINE-1s in different EPHA3 introns. Finally, hypermethylation of some LINE-1s can be found sporadically in cancer. In conclusion, even though the global hypomethylation process that occurs in cancerous cells can generally deplete LINE-1 methylation levels, LINE-1 methylation can be influenced differentially depending on where the particular sequences are located in the genome.

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Related in: MedlinePlus

COBRALINE-1 and CU-Ls correlation. Pearson correlation coefficient values between LINE-1 and genome-wide loci of (A) WSU-HN cells and (B) NOE cells. Arrows indicate an association between loci L1-EPHA3-IVS5 and L1-EPHA3-IVS15.
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Figure 5: COBRALINE-1 and CU-Ls correlation. Pearson correlation coefficient values between LINE-1 and genome-wide loci of (A) WSU-HN cells and (B) NOE cells. Arrows indicate an association between loci L1-EPHA3-IVS5 and L1-EPHA3-IVS15.

Mentions: We evaluated the directions of relationships between methylation levels of two that were between genome-wide and a specific locus or between two loci. Correlations are reported as Pearson correlation coefficients (r). The r-values between −0.5 and 0.5 were considered not significant. The multiple white spots in Figure 5 represent r-values between the COBRAs, listed on the x-axis, and the other r-values. We observed positive correlations between LINE-1 methylation levels between genome-wide and a specific locus or between two loci more frequently in WSU-HN than in NOE cells. This is demonstrated by the fact that most r-values between the LINE-1s of WSU-HN cells, but not of NOE cells, are frequently closer to one (Figure 5A and B). Hence, methylation levels of LINE-1s in cancer cells may result from a generalized process of global demethylation. However, methylation of certain loci, such as L1-SPOCK3 and L1-PKP4, did not have a positive correlation with their cancer genome or other loci (Figure 5A). Interestingly, both of the loci had less hypomethylation in many samples (Figure 4B). Therefore, they may be less influenced by the global hypomethylation process. The highest correlation value observed in cancerous cells, was between the two LINE-1s inserted in the same gene, L1-EPHA3-IVS5 and L1-EPHA3-IVS15 (P < 10−16; Pearson r = 0.913) (Figure 5A). These characteristics of CU-L1 methylation levels suggest that loss of LINE-1 methylation in cancers, in addition to being a result of genome-wide hypomethylation, may also be influenced by locus-specific pressure.Figure 5.


LINE-1 methylation patterns of different loci in normal and cancerous cells.

Phokaew C, Kowudtitham S, Subbalekha K, Shuangshoti S, Mutirangura A - Nucleic Acids Res. (2008)

COBRALINE-1 and CU-Ls correlation. Pearson correlation coefficient values between LINE-1 and genome-wide loci of (A) WSU-HN cells and (B) NOE cells. Arrows indicate an association between loci L1-EPHA3-IVS5 and L1-EPHA3-IVS15.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2553567&req=5

Figure 5: COBRALINE-1 and CU-Ls correlation. Pearson correlation coefficient values between LINE-1 and genome-wide loci of (A) WSU-HN cells and (B) NOE cells. Arrows indicate an association between loci L1-EPHA3-IVS5 and L1-EPHA3-IVS15.
Mentions: We evaluated the directions of relationships between methylation levels of two that were between genome-wide and a specific locus or between two loci. Correlations are reported as Pearson correlation coefficients (r). The r-values between −0.5 and 0.5 were considered not significant. The multiple white spots in Figure 5 represent r-values between the COBRAs, listed on the x-axis, and the other r-values. We observed positive correlations between LINE-1 methylation levels between genome-wide and a specific locus or between two loci more frequently in WSU-HN than in NOE cells. This is demonstrated by the fact that most r-values between the LINE-1s of WSU-HN cells, but not of NOE cells, are frequently closer to one (Figure 5A and B). Hence, methylation levels of LINE-1s in cancer cells may result from a generalized process of global demethylation. However, methylation of certain loci, such as L1-SPOCK3 and L1-PKP4, did not have a positive correlation with their cancer genome or other loci (Figure 5A). Interestingly, both of the loci had less hypomethylation in many samples (Figure 4B). Therefore, they may be less influenced by the global hypomethylation process. The highest correlation value observed in cancerous cells, was between the two LINE-1s inserted in the same gene, L1-EPHA3-IVS5 and L1-EPHA3-IVS15 (P < 10−16; Pearson r = 0.913) (Figure 5A). These characteristics of CU-L1 methylation levels suggest that loss of LINE-1 methylation in cancers, in addition to being a result of genome-wide hypomethylation, may also be influenced by locus-specific pressure.Figure 5.

Bottom Line: Therefore, the loss of genome-wide methylation in cancerous cells occurs as a generalized process.However, different LINE-1 loci showed different incidences of HNSCC hypomethylation, which is a lower methylation level than NOE.In conclusion, even though the global hypomethylation process that occurs in cancerous cells can generally deplete LINE-1 methylation levels, LINE-1 methylation can be influenced differentially depending on where the particular sequences are located in the genome.

View Article: PubMed Central - PubMed

Affiliation: Inter-Department Program of BioMedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.

ABSTRACT
This study evaluated methylation patterns of long interspersed nuclear element-1 (LINE-1) sequences from 17 loci in several cell types, including squamous cell cancer cell lines, normal oral epithelium (NOE), white blood cells and head and neck squamous cell cancers (HNSCC). Although sequences of each LINE-1 are homologous, LINE-1 methylation levels at each locus are different. Moreover, some loci demonstrate the different methylation levels between normal tissue types. Interestingly, in some chromosomal regions, wider ranges of LINE-1 methylation levels were observed. In cancerous cells, the methylation levels of most LINE-1 loci demonstrated a positive correlation with each other and with the genome-wide levels. Therefore, the loss of genome-wide methylation in cancerous cells occurs as a generalized process. However, different LINE-1 loci showed different incidences of HNSCC hypomethylation, which is a lower methylation level than NOE. Additionally, we report a closer direct association between two LINE-1s in different EPHA3 introns. Finally, hypermethylation of some LINE-1s can be found sporadically in cancer. In conclusion, even though the global hypomethylation process that occurs in cancerous cells can generally deplete LINE-1 methylation levels, LINE-1 methylation can be influenced differentially depending on where the particular sequences are located in the genome.

Show MeSH
Related in: MedlinePlus