Gene mutant dosage is associated with prognosis and metastatic tropism in 60,000 clinical cancer samples

The intricate interplay between somatic mutations and copy number alterations critically influences tumour evolution and patient prognosis. However, traditional genomic analyses often treat these alterations independently, overlooking gene mutant dosage - a key emergent property of their interaction. Here, we develop an innovative computational framework that infers mutation copy number and multiplicity directly from clinical targeted sequencing panels without requiring matched normal samples. Using this approach, we derived gene mutant dosage statistics for over 500,000 mutations across 60,000 clinical samples spanning 39 cancer types. By stratifying more than 20,000 patients according to m