Researchers at Mount Sinai’s Tisch Cancer Institute have discovered a new gene that is crucial to the development of colon cancer and established that inflammation in the region surrounding the tumor can contribute to the development of tumor cells. The researchers published their findings in the journal Nature Communications in October 2022.
Researchers at Mount Sinai Identify New Gene That Drives Colon Cancer
Video Credit: Mount Sinai Health System
The “super enhancer,” a complicated region of DNA with a lot of transcriptional machinery that determines whether a cell is malignant, can be programmed by the environment around a colon cancer tumor for the first time, according to research.
The PDZK1IP1 gene, which was not previously recognized as a cancer gene, is controlled by this super enhancer, which is the largest 1-2% of all enhancers in the cell. Colon cancer growth was inhibited when PDZK1IP1 was removed, indicating that PDZK1IP1 and its super enhancer could be targets for cancer treatments.
In the United States, colon cancer is the third most prevalent and second most deadly cancer. This cancer is reliant on surgery for treatment, and immunotherapies that have revolutionized the treatment of advanced cancer have only worked for a small subset of colon cancer patients. That is why there is a great need for novel target identification.”
Royce Zhou. Study First Author and MD/PhD Student, Icahn School of Medicine at Mount Sinai
According to this study, the tumor microenvironment’s surrounding inflammation activates the super enhancer, which is the largest 1–2% of all cell enhancers. The inflammation makes it possible for the cancer cells to survive where they otherwise would not be able to.
Colon cancer risk factors include inflammatory bowel disease; this discovery could help in understanding the mechanism at work.
What this means for most patients with colon cancer is that inflammation that is occurring in the tumor is contributing to the tumor’s growth. This stresses the importance of understanding what we can do to curb the inflammatory effects in the colon through prevention or understanding what dietary effects might have on the microenvironment in the colon.”
Ramon Parsons, Study Senior Author and Director, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Dr Parsons added, “In terms of treatment, we have genetic evidence that targeting this gene actually inhibits tumors. By understanding all these different components, we will have better tools to try to prevent the disease.”
This discovery was made feasible by examining live tumor tissue and surrounding healthy tissue right after surgery on 15 colon cancer patients. According to Mr Zhou, the ability to prepare and examine live cells enables researchers to understand the tumor microenvironment and the genetic and biological reasons for colon cancer.
Dr Parsons further stated, “We had live specimen live cells straight from the operating room that allowed us to immediately measure the epigenetic state of that tumor. Without that infrastructure here at Mount Sinai, we couldn’t have made this discovery.”
Zhou, R. W., et al. (2022). A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma. Nature Communications. doi.org/10.1038/s41467-022-33377-8