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WIREs Nanomed Nanobiotechnol
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Using nanobiotechnology to increase the prevalence of epigenotyping assays in precision medicine

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Epigenetic silencing of genes that are important for DNA repair, cell cycle control, apoptosis, and cellular interactions with the extracellular matrix has been causally linked to several subtypes of cancer. Translating this knowledge of the implications of promoter methylation to wide and routine use in clinical pathology laboratories has been more challenging than the case of genetic analyses because epigenetic modifications do not change the underlying sequence of the affected nucleic acid, rendering polymerase chain reaction analysis alone uninformative. Two epigenotyping assays that detect promoter methylation are currently standard of care in treatment of two distinct tumor types in only a few top hospitals across the United States. Both rely on a harsh chemical step that degrades over 90% of tumor DNA samples, which are often available in limited quantities, and imparts the potential for false‐negative or false‐positive results if the reaction conditions are not exactly correct. Using nanotechnology and biotechnology to devise practical new analysis techniques that avoid the drawbacks of current techniques represents a powerful approach that is likely to significantly increase the clinical use of this class of biomarkers in the coming years. WIREs Nanomed Nanobiotechnol 2017, 9:e1407. doi: 10.1002/wnan.1407 This article is categorized under: Diagnostic Tools > Biosensing Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
A diagram of the methylation‐specific fluorescence in situ hybridization (meFISH) protocol. After a standard fluorescence in situ hybridization procedure is performed, osmium tetroxide is used to crosslink the bipyridine‐modified probe to a methylated CpG. Without a methylated cytosine present, the crosslinking does not occur and the probe is removed upon DNA denaturation. (Reprinted with permission from Ref . Copyright 2013 Oxford University Press)
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A diagram showing sequence‐specific methylation detection by capture of the target sequence on a biochip, methyl‐binding domain binding, and radical photopolymerization. (Reprinted with permission from Ref . Copyright 2014 Royal Society of Chemistry)
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A schematic showing a method of sequence‐specific methylation detection based on the change in photoelectrochemical response upon methyl‐binding domain and an anti‐His‐tag antibody binding. (Reprinted with permission from Ref . Copyright 2014 Elsevier)
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A schematic demonstrating the DNA amplification and signal generation steps of the QuARTS (quantitative allele‐specific real‐time target and signal amplification) assay performed on bisulfite‐treated DNA. (Reprinted with permission from Ref . Copyright 2012 American Association for Clinical Chemistry)
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A schematic demonstrating the general workflow once a glioblastoma sample is obtained. For other cancers, the number and type of molecular diagnostic tests routinely performed may differ. The most clinically feasible diagnostic tests should be compatible with a small section of formalin‐fixed tissue.
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Diagnostic Tools > Biosensing

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