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BioMed Central Blog

Tuesday Jan 10, 2012

DNA methylation of drug transporter gene might explain chemoresistance in liver cancer

Hepatocellular carcinoma is the third highest cause of cancer-related death world-wide. Although several treatments are available – and many more are undergoing clinical trials – drug resistance is a problem in some cases.

In the latest issue of Genome Medicine, Matthias Schwab and colleagues show for the first time that there is a link between the level of expression of the chemotherapy drug transporter SLC22A and DNA methylation. This finding  might explain reduced drug responses in liver cancer and provide a new approach for treating patients.

The team looked at the methylation patterns in the 5' end of three genes encoding organic cation transporters (SLC22A1, SLC22A2 and SLC22A3) in liver samples taken from people with hepatocellular carcinoma and compared them with normal livers.  A state-of-the-art mass spectrometry approach was used to examine DNA methylation.

They found that decreased expression of SLC22A1 in hepatocellular carcinoma correlated with increased methylation of the SLC22A1 gene, and suggests that SLC22A1 is epigenetically regulated.

The good news is that epigenetic modifications are reversible and so pretreatment with a chemical to reduce methylation might result in improved chemotherapy.


 

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