Bachelor of Arts [B.A] [Media and Environmental Communication] From University of Brighton

Many CpG islands associated with transcription of a wide variety of genes become aberrantly methylated in tumours. Genes representing all the classic hallmarks of cancer can become aberrantly methylated as well as genes having a role in response to chemotherapy.

DNA methylation occurs predominantly at CpG sites in the mammalian genome by the DNA methyltransferase (DNMT) enzymes. The interaction of methylated DNA with proteins that detect methylated DNA and other chromatin remodeling proteins render an altered chromatin configuration that prevents the expression of a gene. DNA methylation plays an important role in the expression of oncogenes, tumour suppressor genes and only recently it has also been shown that drug metabolising enzymes (DMEs) are affected by the DNA methylation process. Aberrant alterations in the methylation status of CpG dinucleotides, target sites for DNMT, have been shown in the promoter regions of DMEs but very little literature is available on ALDHs.

Aldehyde dehydrogenases (ALDHs) belong to a class of DMEs, which catalyse the oxidation and detoxification of reactive endogenous and exogenous aldehydes into carboxylic acids via NAD+ coupled reduction (Fig. 3). ALDH1 has been widely studied and is considered a marker of normal and malignant human mammary stem cells and has been shown to be predictive of poor clinical outcome. Increased expression of cytosolic ALDH has been implicated as a mechanism whereby tumour cells may escape the lethality of cytotoxic anticancer alkylating agents, such as cyclophosphamide and related congeners.