Inside our cells, strands of DNA wrap around spool-like histone proteins to form a DNA-histone complex called chromatin. Bradley Bernstein, a pathologist at Massachusetts General Hospital, Harvard University, and Broad Institute, has always been fascinated by this process. What interests him is the fact that an approximately 6-foot-long strand of DNA can be folded and packed into orderly chromatin structures inside a cell nucleus that’s just 0.0002 inch wide.
Bernstein’s fascination with DNA packaging led to the recent major discovery that, when chromatin misfolds in brain cells, it can activate a gene associated with the cancer glioma . This suggested a new cancer-causing mechanism that does not require specific DNA mutations. Now, with a 2016 NIH Director’s Pioneer Award, Bernstein is taking a closer look at how misfolded and unstable chromatin can drive tumor formation, and what that means for treating cancer.
Caption: Oncologists review a close-up image of a brain tumor (green dot). Credit: National Cancer Institute
Scientists have spent much time and energy mapping the many DNA misspellings that can transform healthy cells into cancerous ones. But recently it has become increasingly clear that changes to the DNA sequence itself are not the only culprits. Cancer can also be driven by epigenetic changes to DNA—modifications to chemical marks on the genome don’t alter the sequence of the DNA molecule, but act to influence gene activity. A prime example of this can been seen in glioblastoma, a rare and deadly form of brain cancer that strikes about 12,000 Americans each year.
In fact, an NIH-funded research team recently published in Nature Communications the most complete portrait to date of the epigenetic patterns characteristic of the glioblastoma genome . Among their findings were patterns associated with how long patients survived after the cancer was detected. While far more research is needed, the findings highlight the potential of epigenetic information to help doctors devise more precise ways of diagnosing, treating, and perhaps even preventing glioblastoma and many other forms of cancer.