Post by Harvard Medical School

For decades, scientists have wondered: Does a genetic defect found in nearly all human colorectal cancers simply accompany the disease, or does it trigger its development? A team led by Harvard Medical School researchers at Beth Israel Deaconess Medical Center has now shown that replicating the genetic defect by deleting the gene COSMC (C1GalT1C1) in cells lining the intestines of mice led to the development of invasive colorectal cancer within a year. “We’ve demonstrated that losing this single gene is enough to trigger the entire disease process,” said senior author Richard Cummings, HMS professor of surgery and division chief of Surgical Sciences at Beth Israel Deaconess. In the study, deletion of COSMC led to an array of changes in the cells’ characteristics and behavior. The majority of the mice developed colorectal adenocarcinomas, some of which were invasive. The tumors occurred in the rectum and lower colon of the animal models — the same region where most human colorectal cancers occur. In this image, green and red indicate abnormal expression of cancer-associated growth factor pathways in mouse rectal cells. When COSMC fails, a common marker of cancer known as the Tn antigen appears on the cell surface. The team’s laboratory analyses confirmed that all the tumors in the study expressed the Tn antigen. Because the Tn antigen appears on the surface of cancer cells but not on healthy cells, it represents a promising target for precision therapy. Although researchers are still investigating numerous causes and risk factors of colorectal cancer, if the team’s finding translates to humans, it could inform new strategies to combat the third most commonly diagnosed cancer in the United States. Read more about the research: https://bit.ly/4mHQ2T3