Researchers Create Novel Cell Model of Aging-Related Colon Cancer Risk

A study of lab-grown mouse cells called "organoids" published in Cancer Cell adds significant evidence that epigenetic changes common to aging are critical to triggering colon cancer initiation, reports Medical Xpress . The researchers' lab model mimicked alterations more likely to cause cancer in colon cells over time, and determined epigenetic changes defined by changes in DNA methylation are essential to cancer initiation. Known cancer-driving gene mutations in the model did not cause colon cancers to form, unless epigenetic DNA methylation changes were present as well. The researchers utilized mouse colon organoids derived from six- to eight-week-old specimens, comparing organoids with and without mutations in the BRAFV600E, a cancer-initiating genetic mutation especially common to right-sided colon cancer in humans. "As the organoids aged, they remained genetically stable but became epigenetically unstable, even without the BRAF mutation being introduced," said Johns Hopkins' Hariharan Easwaran. Acquired DNA methylation during "aging" of the organoids suppressed cancer-protective genes in a pattern similar to human aging associated with risk for colon cancer by decade. "Our study indicates that promoter DNA methylation-mediated silencing for important stem cell regulator genes play critical roles in allowing the BRAF mutant oncogene to initiate cancer," Easwaran concluded.