New development in DNA modification is a big step forward in combating cancer
Sameen Liaqat CONTRIBUTOR
Alteration of gene expression can be utilized to dysregulate forms of deadly cancer. The study conducted by Yale University and University of California, San Diego researchers directed its focus on the A base in DNA, which is one out of the four genetic letters in DNA that forms its structure. The study demonstrates how a modification of the A base affects tumor stem cells, specifically glioblastoma tumors, an extremely fatal form of brain cancer.
This breakthrough can be important in explaining the fatal nature of glioblastoma that can leave patients with a mere three to six months of life. Targeting the A base in DNA glioblastoma DNA models resulted in a longer survival rate of mice that had gliomas from humans surgically transplanted in them. This suggests that this alteration in the gene expression is a prospective glioblastoma treatment.
Dot blot analysis was performed in order to examine the role of the A base DNA by extracting human-derived glioblastoma stem cells. The results presented a dramatically preeminent level of A base DNA in the glioblastoma stem cells in relation to normal human cells.
The research points out that the A base alteration can be detected early on in embryonic growth and is fundamental in this development process. However, this alteration dissolves in adult life, thus the lack of attention attributed to this modification in regards to cancer so far. Nonetheless, Yale Cancer Center researcher and co-corresponding author of the study, Andrew Xiao, said that the cancer is abundant in the A base in glioblastomas, distinguishing it from other cases.
Previous studies related to this topic concerned histone function in the regulation of DNA methylation and presented how histone function levels were distorted when DNA methylation was completely removed. This research confirms the possibility of an interaction between the A base and histone function and their potential collaboration. Collaboration between these two forms of alteration can influence transcription, the initiating step of gene expression, by impeding this step in human cancers.
This means that the A base makes for an appealing target for developing cancer drug therapies, as there have been several hundred modified A bases in tumors while there are barely any in standard brain tissue.
The focus of this research is glioblastoma tumors, but if proven successful, this can lead to more innovative methods to treat cancers that in the present are still incurable.
Essentially, this research demonstrates that in human tissue, A base DNA modifications exist and are regulated by enzymes, and maintaining this regulation is crucial for cell survival and growth. Because of this research and its finding of a new category of DNA modification, further studies and research can use this information in order to “identify a potential therapeutic vulnerability that can be exploited for cancer therapy.”
This research was conducted by a number of key figures in the field including Tao P. Wu of Yale who was a co-author of the study. The corresponding author of the research was Jeremy N. Rich, from the Department of Neuroscience at the University of California.
This research was possible due to the funds provided by the National Institutes of Health grants for Xiao and Rich’s labs. Xiao’s lab also received an award from the Ludwig Family Foundation, which partially contributed to the funding of this research.