Shared inheritance reveals landscape of somatic and germline cancer risk in TP53

MacGregor et al. distinguish germline from somatic TP53 variants in 469,391 individuals using shared haplotype segments. Classic Li-Fraumeni alleles detected in healthy blood appear to be mostly somatic clonal expansions conferring largely hematological cancer risk, showing that somatic rather than germline risk predominates in cancer-free middle-aged adults.