TET Enzymes Deficiency Increases the Risks of Developing Cancer According to Northwestern University Study

By Eziokwu Fab-Emerenini MBBS | Published on January 21, 2022
Reviewed By Gilmore Health | On: May 17, 2023

New studies have related the development of various cancers to DNA manifesting itself as knot-like folds and third rungs between both strands of the double helix. There is also evidence citing the involvement of a key enzyme that has regulatory roles when it comes to the formation of the irregular structures of cancer. Cancer

TET-enzymes

TET-enzymes belong to a family of enzymes that play key roles in the removal of methylation marks from DNA. Removal of these TET-enzymes can also cause backlogs in the interactions between cells. A reduction in the functionality of TET-enzymes is implicated in a plethora of the various forms of cancers and this phenomenon is particularly linked to B-cell lymphoma.

The discovery of these enzymes was by scientists in Northwestern Medicine and the La Jolla Institute for Immunology (LJI) and their research was published and disseminated in the Nature Immunology Journal.

It is crucial to try and comprehend how cancers develop following the destruction of TET-enzyme functionality, as this will help in the progression of novel drug treatment of cancer.

Before their discovery, the linkage of both hazardous cell characteristics was yet to be made.

The appearance of alien and irregular structures in the DNA

After the loss of TET-enzymes, genomic volatility occurs in the TET deficient cells. The research into the relationship between TET deficiency and genomic volatility was carried out by Vipul Shukla, an assistant professor of the biology of cell and development at the Northwestern University, Feinberg school of medicine, in association with Anjana Rao, a professor at LJI center for cancer immunotherapy, and Daniela Samaniego-Castruita, a graduate of the University of California, San Diego.

In their research, the scientists first erased two types of TET-enzymes (TET-enzyme 2 and TET-enzyme 3) gotten from the mature B-cells of mice. B-cells are a class of white blood cells with immunological functions. They help produce antibodies for our body’s immunological defense system and they function to guard our bodies and prevent us from catching infections. According to Shukla, the research conducted shows that erasing the TET-enzymes had colossal involvements in disrupting the homeostasis and internal milieu of the B-cells, and with the disruption came the appearance of genomic volatility.

According to Samaniego-Castruita, the TET deficient mice started developing lymphoma, and other features implicated in genomic volatility, like double-stranded pauses in DNA were also observed.

The research team also further observed indications of things that were occurring at the elemental molecular level by carrying out a genomic analysis which revealed that in the absence of TET-enzyme 2 and TET-enzyme 3, there was littering of the DNA of B-cells with irregular cellular components like G-quadruplexes and R-loops.

These cellular components make the reading of DNA code and the ‘unzipping’ of DNA strands difficult.

A function of the progression of B-cell lymphoma

In Shukla’s quest to understand why the cellular components mentioned above were shown at all so his research team could understand how to prevent their formation, they observed one of the regulatory enzymes, the DNMT-1 which appeared to be altered in correspondence to the level of the TET-enzymes.

They observed that in TET deficient cells, there were higher levels of DNMT-1 in those cells and the increased levels of the DNMT-1 functioned to maintain DNA methylation.

Further research showed that deleting DNMT-1 enzymes was implicated in delays in the progression of malignant B-cell lymphomas, and also subpar levels of G-quadruplexes and R-loops.

There is a belief that regulating G-quadruplexes and R-loops by TET-enzymes might be one way of controlling genomic volatility.

Clinical Significance

The loss of TET-enzymes can lead to the development of various forms of cancers, particularly B-cell lymphoma.

Another important clinical significance is the discovery that the levels of DNMT-1, a regulatory enzyme, were shown to be elevated in TET-enzyme deficient cells. The increased amount of DNMT-1 in these cells was discovered to be of great help in maintaining DNA methylation.

Conclusion

More research is still ongoing but the findings show that loss of TET-enzymes is one of the reasons for the development of cancers and that DNMT-1 enzymes propound this phenomenon by helping to maintain DNA methylation.

To curb genomic volatility, more research should be done into regulating G-quadruplexes and R-loops by TET enzymes.