Hypomethylation of the DNMT3L promoter in ocular surface squamous neoplasia

Ophthalmic Pathology Services, Kallam Anji Reddy Campus, L. V. Prasad Eye Institute, Hyderabad, India.
Archives of pathology & laboratory medicine (Impact Factor: 2.84). 08/2010; 134(8):1193-6. DOI: 10.1043/2009-0417-OA.1
Source: PubMed

ABSTRACT Cancer is known to have epigenetic inputs, with events like genomewide hypomethylation and gene-specific hypermethylation of DNA. The DNA methyltransferase enzymes act as effectors of this reprogramming. A previous study revealed that hypomethylation at the DNA methyltransferase 3-like (DNMT3L) promoter could be a potential biomarker in cervical tumors. Because the pathobiology of ocular surface squamous neoplasia (OSSN) is similar to that of cervical tumors, we wanted to determine whether similar changes occur in the methylation pattern at the DNMT3L promoter in OSSN.
To evaluate the methylation status of the DNMT3L promoter in OSSN compared with healthy conjunctiva.
We evaluated DNA methylation at the DNMT3L promoter in the tumor tissues of 6 patients with histologically proven OSSN and in healthy conjunctiva tissue from 7 individuals for controls using the sodium bisulfite-assisted conversion of genomic DNA. Extracted genomic DNA was treated with sodium bisulfite and amplified with specific primers for the DNMT3L promoter region. The specific polymerase chain reaction products were cloned and sequenced.
The mean age of these patients was 50.2 years (range, 35-65 years). Histologically, 4 OSSN cases were invasive; 2 were intraepithelial. Healthy conjunctival tissues exhibited a methylated promoter region, whereas a variable loss of methylation was observed in all 6 OSSN cases.
We have, for the first time to our knowledge, identified loss of methylation at the DNMT3L promoter in OSSN cases, but its physiologic significance is yet to be understood. Further studies are warranted to substantiate our results.

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Available from: Guru Prasad Manderwad, Jan 28, 2015
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    • "It has been suggested that regions that show interaction with both PRC1 and PRC2 complexes have epigenetic regulatory properties and are part of large CpG islands [41]–[43]. DNMT3L DMC, which is part of a CpG island, is methylated in most somatic tissues [15]–[17] and we show here it interacts with PRC1, PRC2 and PhoRC polycomb repressive complexes. This would indicate that DNMT3L DMC possess essential attributes of a regulatory element. "
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