Oncogenic composite mutations can be predicted by co-mutations and their chromosomal location.

ABSTRACT: Genetic heterogeneity in tumors can show a remarkable selectivity when two or more independent genetic events occur in the same gene. This phenomenon, called composite mutation, points toward a selective pressure, which frequently causes therapy resistance to mutation-specific drugs. Since composite mutations have been described to occur in sub-clonal populations, they are not always captured through biopsy sampling. Here, we provide a proof of concept to predict composite mutations to anticipate which patients might be at risk for sub-clonally driven therapy resistance. We found that composite mutations occur in 5% of cancer patients, mostly affecting the PIK3CA, EGFR, BRAF, and KRAS genes, which are common precision medicine targets. Furthermore, we found a strong and significant relatio

SUBMITTER: Kucukosmanoglu A 

PROVIDER: S-EPMC11459034 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature