West LA Times

A groundbreaking study conducted by researchers at the University of California, Los Angeles (UCLA) has revealed a significant connection between mutations in noncoding DNA and genes associated with cancer pathways, as well as their impact on cancer patient survival.

According to corresponding author Xinshu “Grace” Xiao, a UCLA professor of integrative biology and physiology, the research aimed to address the challenge of understanding the functions of mutations in noncoding regions. Xiao explained, “Predicting the outcomes of mutations in protein-coding regions is relatively straightforward, but understanding the functions of mutations in noncoding regions presents a significant challenge.”

Through an experiment that involved synthesizing thousands of mutations into fully functioning DNA reporters, the researchers were able to analyze the alterations in mRNA abundance. The study, published in the journal Nature Communications, uncovered that mutations in noncoding regions can lead to abnormal amounts of messenger RNA (mRNA), which plays a crucial role in protein production within cells.

Ting Fu, the first author of the article and a postdoctoral scholar in Xiao’s lab, highlighted a key finding from the research, stating, “The number of functional mutations in untranslated regions can predict patient survival for certain cancer types.” This discovery led to the introduction of a new metric called ‘untranslated tumor mutation burden’ (uTMB), which showed a strong association with lung squamous cell carcinoma and head and neck squamous cell carcinoma.

The implications of this research are profound, as the identification of these mutations in noncoding regions offers new possibilities for the development of prognostic testing tools. By calculating uTMB for individual patients, healthcare professionals could potentially predict survival outcomes and make informed decisions regarding treatment options.

Moreover, the study sheds light on the intricate processes that drive cancer progression by understanding how mutations in noncoding DNA influence mRNA abundance and, consequently, protein production. Xiao emphasized the importance of further research into the regulatory mechanisms of these mutations, stating, “Our next objective is to unravel the precise regulatory mechanisms by which these mutations function in cancer cells. Given their impact on mRNA levels, the underlying mechanisms could hold critical importance for the advancement of cancer treatment.”

The study was supported by grants from the National Institutes of Health, underscoring the significance of the findings in advancing our understanding of the role of mutations in noncoding DNA in cancer pathways and patient outcomes.