Biomarker links cancer to problems with human genome

"The research highlights the broader implications of the importance of genome stability for our health."

By YAFIT OVADIA
Updated: JANUARY 21, 2019 18:50
Tel Aviv University Sackler School of Medicine (photo credit: PIKI WIKI)
Tel Aviv University Sackler School of Medicine
(photo credit: PIKI WIKI)
A study conducted at Tel Aviv University (TAU) revealed that amounts of a certain protein can lead to instability of the human genome, and in turn show that certain DNA markers work as a precursor for cancer.
Human DNA can be affected by anything, from the air that we breathe, food that we eat and even substances in the environment, such as radiation. All of these can lead to mutability of the human genome, causing genetic disorders, some chronic diseases and even cancer.
A study conducted by researchers at TAU showed high levels of ubiquilin-4 - a protein, that is a marker for instability of the genome. This protein helps protect the genome against DNA damage, but high levels can be detrimental. As the levels increase in tumor cells, this can lead to genome instability, making tumors grow in size and be resistant to current treatments.
Prof. Yossi Shiloh, Dr. Yael Ziv and doctoral student Bhavana Velupula of the Department of Human Molecular Genetics and Biochemistry at the Sackler School of Medicine in TAU worked with Dr. Ron Jachimowicz and Prof. Christian Reinhardt of the University of Cologne, as well as with Dr. Dave Hoon of the John Wayne Cancer Institute in Santa Monica, California.
Prof. Shiloh stated: "This novel biomarker provides new, critical information about the tumor stage... as well as the patient's chances of responding to treatment, adding that "tumors with high levels of ubiquilin-4 may be more resistant to radiation and some chemotherapies than those with normal levels of this protein. But the good news is that they may also respond better to other types of cancer therapy."
He continued, saying, "The importance of maintaining genome stability and integrity has been demonstrated through the study of rare genetic disorders, but genome stability has now become a public health issue. There are so many proteins involved in responding to DNA damage, and behind every protein is a different gene. There are infinite ways in which a gene can mutate. Various combinations of these mutations may lead to chronic diseases and a predisposition to cancer."
Damage to DNA causes the body to respond by aiming to preserve the stability of the genome amid threats, leading the body to release proteins that try to protect the genome from further damage.
In 1995, Shiloh's team uncovered the gene coding of a major site that has been proven to lead to genome instability - the protein ataxia-telangiectasia mutated (ATM) that is a precursor to the genome instability syndrome, ataxia-telangiectasia (A-T).
ATM is also related to the body's response to such damage, enacting a network in response to tears in the DNA molecule. This causes slight chemical changes in some proteins, turning them into reserve proteins, which prevent them from performing damage control.
The team also revealed that the shortage of ubiquilin-4 can cause genome instabilities as well.
Prof. Shiloh added: "The research highlights the broader implications of the importance of genome stability for our health."