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Cancer Methylation May Produce Easily Assayed Changes to DNA Polymer Properties

NEW YORK (GenomeWeb) – An Australian research team has proposed that methylation landscape shifts, and corresponding physical and chemical changes to DNA, may serve as the basis for an assay for multiple cancer types.

"Virtually every piece of cancerous DNA we examined had this highly predictable pattern," corresponding author Matt Trau, a researcher with the University of Queensland's Center for Personalized Nanomedicine, said in a statement, calling it a "starting discovery."

In a paper published in Nature Communications yesterday, Trau and his colleagues outlined their strategy, which involved profiling the so-called cytosine methylation "Methylscape" in prostate tissue samples from a healthy individual and an individual with metastatic prostate cancer, alongside transmission electron microscopy images of purified genomic DNA from these samples.

The study hinged on the notion that epigenetic reprogramming alters the Methylscape of many cancer types, the authors explained, prompting interest in a way to quickly and reliably detect this biomarker.

Rather than developing an assay to assess methylation in each suspected cancer sample, they hypothesized that the "different methylation landscape of normal and cancerous epigenomes may impact their physicochemical and self-assembly properties in aqueous solutions, and as they interact with solid surfaces."

Indeed, the team detected changes to the behavior of the DNA polymer in the presence of cancer-related methylcytosine shifts, which altered the way cancer DNA molecules interacted with gold surfaces. Using these insights, the group came up with electrochemical or color-based assays for the proposed "cancer DNA" nanostructures, including an assay involving gold nanoparticles intended to quickly change color in the presence of cancer DNA.

When the researchers applied this approach to genomic DNA isolated from dozens of cell line, tissue, or cell-free circulating DNA samples — representing healthy tissues as well as breast, prostate, lymphoma, lung, or colorectal cancers — they found that the assays could detect cancer with accuracy that neared 90 percent, in some cases.

In a statement, co-first author Abu Ali Ibn Sina, a post-doctoral researcher in Trau's University of Queensland lab, said that the approach "could be a game-changer in the field of point-of-care cancer diagnostics," since it appears that the DNA nanoparticle-based assays would be applicable to tissue-derived DNA or cell-free DNA circulating in the blood.

While it remains to be seen how well the approach works across all cancer types, Trau said the proposed signature "looks really interesting as an incredibly simple universal marker of cancer" that could potentially be applied diagnostically in as a "very accessible and inexpensive technology that does not require complicated lab-based equipment like DNA sequencing."