Scientists identify important genes that are turned on in most types of cancer

Credits: Suzanna Hamilton, Broad Communications

Doctors at the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute have found that a gene called FOXR2, which is normally turned off in most tissues in the body, is activated in at least 70% and 8% of cancer types. I found that it will be done. Individual tumors.

Their research has recently Cancer research, Can help scientists better understand how different cancers develop. The research team has already begun working with chemists and structural biologists to find ways to target this gene with new therapies.

“The fact that this gene is usually turned off in most tissues means that it may be possible to target it in a way that does not cause many side effects,” said Broad and Dana-Farber’s children. Neuro-oncologist.

Find FOX R2

Dana-Farber’s pediatric oncologist and first author of this paper, Jessica Tsai, a postdoctoral fellow in Bandopadhayay’s lab, is called diffuse midline glioma (a deadly tumor in the center of the brain). I was analyzing the genome sequence of a kind of pediatric brain tumor. Surprisingly, she and her team found that many cancers showed abnormal expression of FOXR2. This gene encodes a transcription factor, is located on the X chromosome, and is usually expressed only in the testis.

“In fact, the discovery was striking at first because normal tissues other than the testis should not express FOXR2,” Tsai said.

To look for traces of genes in other cancers, Tsai and her colleagues looked at cancer databases, analyzed human cell cultures, and sequenced tumors from animal models of cancer.They are osteosarcoma, melanoma, and Non-small cell lung cancer— FOXR2 expression and diffuse midline glioma tumors from the Dana-Farber Tumor Bank were also shown. The team worked with David Jones of the German Cancer Research Center to confirm that many types of childhood tumors turn on FOXR2.

“The families who donated these tumors really made it possible to look at genes like FOXR2 and explain their role in these catastrophic brain tumors,” said Bandopadhayay.

Functional clues

In collaboration with Tim Phoenix, a collaborator at the University of Cincinnati, scientists have studied mice with and without activated FOXR2, resulting in gene expression. Brain tumor Includes diffuse midline glioma. They also found that cells activate genes through a process called hypomethylation. Methyl group From the gene.And researchers found that when FOXR2 was active, a group of transcription factors called ETS was overexpressed and probably driving. tumor Formation.

The team believes that FOXR2 may be part of a larger pattern in which the normally inactive testicular gene is turned on in cancer patients. In other studies gene It is abnormally expressed in tumors on the X chromosome, called the cancer testicular antigen. These antigens have become a major target for pharmaceutical companies developing new cancer therapies.

Bandopadhayay and Tsai say their research provides some early clues about how FOX R2 works, but there’s still a lot to learn. Next, they want to break down the relationship between ETS and FOXR2 in order to better understand how genes are activated. The team has also already partnered with other laboratories at the Broad and Dana-Farber Cancer Institute to explore ways to develop cancer treatments that target FOXR2.

Studies have found that “junk” DNA jumps are a new cause of childhood brain tumors

For more information:
Jessica W. Tsai et al, FOXR2, is an epigenetic regulated pan-oncogene that activates the ETS transcription circuit. Cancer research (2022). DOI: 10.1158 / 0008-5472.CAN-22-0671..… Regulated pan-cancer

Quote: Scientists found most cancer types obtained on July 22, 2022 from https: // (July 2022) 22nd) to identify important genes that will be turned on

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Scientists identify important genes that are turned on in most types of cancer

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