Researchers at Children’s Hospital of Philadelphia (CHOP) developed a longitudinal atlas of neuroblastoma, a common and potentially deadly childhood cancer, to gain a deeper understanding into precise molecular mechanisms underlying why and how certain treatments eventually become ineffective.

The findings, which offer insights that could potentially lead to new personalized medicine approaches in neuroblastoma treatment, were published today in the journal Nature Genetics.

Despite significant advances in the standard of care, the 5-year survival rate of high-risk neuroblastoma after diagnosis remains less than 50%. Neuroblastoma cells within the same tumor can vary greatly, which creates challenges in treatment efficacy. Until now, the scientific community lacked understanding of how the tumor microenvironment changes during treatment.

A new multicenter study by researchers at the Icahn School of Medicine at Mount Sinai, in collaboration with the 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.

Published in the April 14 online issue of Cell, the study, “Precision Proteogenomics Reveals Pan-Cancer Impact of Germline Variants,” is the first to detail how millions of inherited genetic differences influence the activity of thousands of proteins within tumors.

Drawing on data from more than 1,000 patients across 10 different cancer types, the research illustrates how a person’s unique genetic makeup can shape the biology of their cancer.

Cells use many complex genetic repair backup systems to fix DNA damage and remain healthy throughout their lives.