Signposts in DNA that Pinpoint Risks for Cancers and other Diseases - Benjamin Tycko, MD @HMHNewJersey

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Benjamin Tycko, MD gives an overview of Signposts in DNA that Pinpoint Risks for Cancers and other Diseases.

By sequencing entire genomes for DNA modifications and analyzing cancer tissues as well as healthy tissues, Hackensack Meridian Health researchers and doctors have detected what may be a key to cancer threats and other diseases: unique DNA locations where certain expression changes (methylation) are imbalanced, according to a new paper.

On June 29, the scientists, from the Center for Discovery and Innovation (CDI), Hackensack University Medical Center and its John Theurer Cancer Center (JTCC), and the Georgetown Lombardi Comprehensive Cancer Center Consortium, recognized by the National Cancer Institute, reported their findings in the global journal Genome Biology.

It may be difficult to identify the most strongly disease-related genetic variants in widespread genome sequencing – but by zooming into main genetic locations associated with these DNA methylation imbalances in multiple normal and cancer tissues, scientists report having discovered promising new leads under the wider statistical signals.

The current research has created one of the largest datasets of high quality used in this kind of approach. Among the DNA samples analyzed were different types of tissue from 89 healthy controls, plus 16 cancer samples from three types of tumors treated at JTCC by oncologists and surgeons: B-cell lymphomas, multiple myeloma, and multiforme glioblastoma (a common and difficult to treat brain tumour).

A total of 15,112 allele-specific methylation sites, including 1,838 located near statistical signals of disease susceptibility from genome-wide association studies (GWAS) were identified by the researchers. These data were made publicly accessible so that new theories could be checked by other scientists in the studies "post-GWAS."

Among its novel results, the paper also describes evidence that non-coding mutations (which do not alter protein sequences) "may play roles in cancer via long-range regulatory effects on gene expression." A particular example cited in the paper is a mutation that induces allle-specific methylation in the TEAD1 gene, which has been shown to be over-expressed in aggressive and treatment-range cancers.

Another finding is that certain disease-relevant genetic variants which exist in "chromatin deserts," places in the DNA that have little to no clear biological signals in available tissue types – but which are identified by the footprints of allel-specific methylation and may have been involved at various times in the cell history to developmental stages.