Impact of Inherited DNA on Cancer Biology Revealed

 


A new multicenter study by researchers at the Icahn School of Medicine at Mount Sinai, in collaboration with the National Cancer Institute-funded Clinical Proteomic Tumor Analysis Consortium (CPTAC) and colleagues around the world, has discovered that the genes we are born with—known as germline genetic variants—play a powerful, underappreciated role in how cancer develops and behaves.


The findings could have major implications for how doctors treat cancer in the future. While current treatments are largely guided by the genetic makeup of a patient’s tumor, this research suggests that looking at a patient’s inherited DNA could further refine diagnosis, risk prediction, and therapy selection.


Until now, most cancer research has focused on somatic mutations—changes that occur in cells over a person’s lifetime. But inherited germline variants outnumber somatic mutations by a wide margin, and their impact on cancer has remained poorly understood, say the investigators.


To conduct the study, the researchers used an advanced technique known as precision peptidomics, which enabled them to examine how specific inherited mutations modulate the structure, stability, and function of proteins in cancer cells. By mapping more than 330,000 protein-coding germline variants, the team uncovered how these inherited differences can alter protein activity, impact gene expression, and even drive how tumors interact with the immune system.


The research adds to growing evidence that personalized cancer care should take into account not just the tumor’s mutations, but the genetic background of the person, too. However, the investigators caution that the study’s findings are based on data from a primarily European-ancestry cohort, and further research is needed to ensure these insights apply across multi-ancestry populations.


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