The epigenome as a molecular marker and target.
Tumor cell proliferation, de-differentiation, and progression depend on a complex combination of altered cell cycle regulation, excessive growth factor pathway activation, and decreased apoptosis. The understanding of these complex mechanisms should lead to the identification of potential molecular markers, targets, and molecular profiles that should eventually expand and improve therapeutic intervention. It now appears clear that methylation plays a central role in transformation, both in vitro and in vivo. However, the exact targets and mechanism(s) are not yet fully understood. This is partly due to the significant number of genes altered by changes in intracellular methyltransferase activity and the chemical agents used to modulate gene expression. The complex nature of methylation's role in regulating gene expression suggests that in addition to investigating individual genes, researchers should develop more comprehensive methods to examine gene expression patterns and their predictive value as this will likely be necessary in the future. If methylation plays a role in transformation, then it seems logical that genes regulating intracellular methylation status may be used as molecular markers to profile tumors by any new methods currently being developed. Perhaps more noteworthy is that DNMT genes may be found to be novel molecular targets for new factor-specific anticancer agents. This idea will be addressed.
Gius
David
D
Molecular Radiation Oncology Section, Radiation Oncology Branch, Radiation Oncology Sciences Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1002, USA. giusd@mail.nih.gov
Bradbury
C Matthew
CM
Sun
Lunching
L
Awwad
Rania T
RT
Huang
Lei
L
Smart
Dee Dee K
DD
Bisht
Kheem S
KS
Ho
Allen S
AS
Nguyen
Phuongmai
P
D001374:Azacitidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D000077209:Decitabine; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D000097584:DNA Methyltransferase 3B
D001374:Azacitidine; D014408:Biomarkers, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000077209:Decitabine; D000097584:DNA Methyltransferase 3B