Emerging role of low-frequency somatic mutations in cancer relapse: from early detection to precision oncology

Somatic mutations with low variant allele frequencies offer a highly sensitive lens for detecting cancer relapse driven by diverse causes, including clonal evolution and therapy resistance. Advances in next-generation sequencing have enabled robust subclonal variant identification that typically fall below conventional detection limits, supporting a comprehensive understanding of individual molecular profiles that can lead to relapse. These low-level alterations frequently emerge before clinical or radiological relapse and can inform response-adaptive treatment decisions. This review integrates the current biological and technical insights into low-frequency mutations and evaluates their emerging roles in tumor relapse management and precision oncology.