Nat Commun: Scientists have identified key new genes driving colon cancer

Tumors tend to exhibit enhanced reprogramming effects compared to normal tissue, and their causes are mainly due to changes in the
cell's internal genome.
Recently, a research report published in the international journal Nature Communications entitled "A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma", Scientists from institutions such as Mount Sinai Medical College have identified a new gene that is important for colon cancer growth, while also finding that inflammation in the external environment around tumors may lead to the growth
of tumor cells.

In this study, the researchers found for the first time that the environment surrounding colon cancer tumors may be able to reprogram so-called "super enhancers," a complex region of DNA with a high concentration of transcriptional machinery
that controls whether cells become malignant.
This super-enhancer, which makes up 1 to 2 percent of all enhancers in cells, regulates the PDZK1IP1 gene, which was previously identified as an oncogene
.
Once the researchers removed the PDZK1IP1 gene, colon cancer growth slowed, which may indicate that PDZK1IP1 and its super-enhancer could be targeted for new anti-cancer therapies
.

Image source: Nature Communications (2022).
DOI:10.
1038/s41467-022-33377-8

Researcher Royce Zhou said: "Colon cancer is the third most popular and the second most deadly cancer in the United States, this cancer relies on surgery for treatment, and the emergence of immunotherapy has completely changed the treatment paradigm of colon cancer patients, but it is only effective for a small percentage of patients, which is why scientists need to identify new targets
.
" ”

The results suggest that super-enhancers may be activated by peripheral inflammation in the tumor microenvironment, which allows cancer cells to survive in an environment where they would not otherwise survive, inflammatory bowel disease is a known risk factor for colon cancer, and this study can also help researchers understand the novel molecular mechanisms of
colon cancer development.
 

Dr.
Ramon Parsons said that for most colon cancer patients, this means that the inflammation that occurs in the tumor promotes tumor growth, which may emphasize the importance of researchers to curb the inflammatory effects in the colon by preventing or understanding the effects of diet on the colon microenvironment.
In terms of treatment, there is now genetic evidence that targeting specific genes can actually inhibit tumor progression, and by understanding all the components, researchers may have special tools to prevent colon cancer as much as possible
.

The findings were made possible by studying biopsy tissue and surrounding healthy tissue from 15 postoperative colon cancer patients, and being able to prepare and analyze living cells may help researchers look at the tumor microenvironment and the genetic and biological drivers that induce colon cancer
.
 

Parsons said that we have living cells from living specimens directly from the operating room, which may allow us to immediately determine the epigenetic state of tumors, which may not be possible
without the basic equipment of Mount Sinai Hospital.
 

In summary, the results of this study emphasize the significance and importance of epigenomic analysis of
original specimens from colon cancer patients.

Original source:

Zhou, R.
W.
, Xu, J.
, Martin, T.
C.
et al.
A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma.
Nat Commun 13, 6041 (2022).
doi：10.
1038/s41467-022-33377-8