Korean researchers have identified a mutation involved in the progression of thyroid cancer, the most common type of cancer in Korea, and clarified how it works.
According to Seoul National University Hospital on the 24th, a joint research team consisting of Professor Lee Kyu-eun of the Department of Breast and Endocrine Surgery, Professor Lee Cheol-hwan of the Department of Pharmacology at Seoul National University College of Medicine, and Professor Ryu Je-kyung of the Department of Physics and Astronomy at Seoul National University uncovered the mechanism of the EZH1 Q571 mutation using thyroid cancer patient tissues and cell lines.
Thyroid cancer is a disease so common that it ranks first in cancer incidence among Koreans. According to national cancer registration statistics released by the Ministry of Health and Welfare and the Korea Central Cancer Registry, the number of thyroid cancer patients as of 2023 was approximately 587,000, accounting for 21.5% of all cancer types, the highest share. The EZH1 Q571R mutation is a type of variant of the EZH1 protein, which is known to suppress gene expression in follicular and oncocytic thyroid cancers. Although it is commonly found in thyroid cancer, how it specifically affects cancer development and progression has not been sufficiently studied.
The research team conducted biochemical, single-molecule, and epigenomic analyses, which showed that the EZH1 Q571R mutation increases enzyme activity and chromatin condensation ability. The team also confirmed that repressive histone marks extended into active histone mark regions, causing the two marks to abnormally coexist. This suggests that the EZH1 Q571R mutation can block the expression of key tumor suppressor genes and promote cancer growth.
These phenomena consistently appeared in actual patient tissues and animal experiments as well. In patient tissues carrying the EZH1 Q571R mutation, the expression of tumor suppressor genes was reduced, and in animal experiments, the presence of the mutation promoted cancer growth by about 34% compared with the normal type.
The research team conducted magnetic tweezers analysis to determine why mutations of EZH2, a protein homologous to EZH1, are not found in thyroid cancer. As a result, the EZH2 Q570R mutation posed a low risk of cancer development because it had a low chromatin condensation ability even when enzyme activity increased. In other words, the team's analysis is that the key to cancer growth lies in chromatin condensation ability.
"Through this study, we confirmed that the EZH1 Q571R mutation blocks the expression of tumor suppressor genes and promotes cancer growth," Professor Lee Kyu-eun stressed. "It is significant in that we identified for the first time that chromatin condensation ability is the key factor governing this."
This study was published in the latest issue of the international journal Molecular Cell.
