The nanotechnology and epigenomics fields are barely 10 years old. Both show enormous future potential. An important application has recently emerged that involves both of them as pointed out in a recent research announcement .
I have discussed DNA methylation several times before. See the blog posts Epigenetics, Epigenomics and Aging and DNA methylation, personalized medicine and longevity in this blog. Also the blog entry Homicide by DNA methylation which discusses the possibility that DNA methylation may be the cause of aging and death in higher organisms. DNA methylation involves the chemical attachment of a methyl group to a cytosine nucleotide in the DNA on chromosomes. DNA methylation happens throughout life and modifies the epigenomic state of a cell, that is, helps determine which genes are turned on and which genes are turned off. In general, methylation silences genes, that is turns them off. When key tumor-suppressor genes are silenced due to methylation, vulnerabilities to cancers exist. Knowledge that tumor suppressor genes are methylated is potentially valuable to alert disease susceptibility and to allow preventive measures to be taken.
Tests for silenced tumor suppressor genes exist but they are awkward, involve multi-step laboratory procedures, and less sensitive than the new method. The new discovery possibly opens the door for widespread economic testing for multiple cancer-related methylation patterns.
“Using tiny crystals called quantum dots, Johns Hopkins researchers have developed a highly sensitive test to look for DNA attachments that often are early warning signs of cancer. This test, which detects both the presence and the quantity of certain DNA changes, could alert people who are at risk of developing the disease and could tell doctors how well a particular cancer treatment is working. — When the quantum dots are exposed to certain types of light, they transfer the energy to fluorescent molecules, shown as pink globes, that emit a glow. This enables researchers to detect and count the DNA strands linked to cancer(ref).”
The new testing method is reported in the paper MS-qFRET: A quantum dot-based method for analysis of DNA methylation in the August issue of Genome Research. Samples were collected by spitting on a chip. “Here we report an ultrasensitive and reliable nanotechnology assay, MS-qFRET, for detection and quantification of DNA methylation. Bisulfite-modified DNA is subjected to PCR amplification with primers that would differentiate between methylated and unmethylated DNA. Quantum dots are then used to capture PCR amplicons and determine the methylation status via fluorescence resonance energy transfer (FRET). Key features of MS-qFRET include its low intrinsic background noise, high resolution, and high sensitivity. This approach detects as little as 15 pg of methylated DNA in the presence of a 10,000-fold excess of unmethylated alleles, enables reduced use of PCR (as low as eight cycles), and allows for multiplexed analyses. The high sensitivity of MS-qFRET enables one-step detection of methylation at PYCARD, CDKN2B, and CDKN2A genes in patient sputum samples that contain low concentrations of methylated DNA, which normally would require a nested PCR approach. The direct application of MS-qFRET on clinical samples offers great promise for its translational use in early cancer diagnosis, prognostic assessment of tumor behavior, as well as monitoring response to therapeutic agents.”
While this post describes a better means for detecting cancer-related DNA methylation, my November 1 post discusses the hope of reversing such methylation once it is detected DNA demethylation – a new way of coming at cancers.
This work is another example of how technologies from diverse disciplines are coming together so as to accelerate the state-of-the-arts of disease prevention, detection, and therapy. And, of course, these will also extend average longevity. Like a multitude of other developments, the practical benefits of the most basic discoveries are probably 4-15 years out. See, for example, yesterday’s post Terminator stem cells in the early pipeline, the December 6 post Personalized medicine and genetic drug interaction, the November 24 post It’s a long way to stem cell treatment, and the November 11 item A gene therapy home run.