A telomere-to-telomere map of somatic mutation burden and functional impact in a cancer.

Near-telomere-to-telomere diploid assembly of a donor paired with deep short- and long-read sequencing of their melanoma shows that 16% of somatic variants fall in sequences absent from GRCh38, with satellite repeats acting as UV mutagenesis hotspots. Centromere kinetochore binding domains are focal sites of chromosome arm aneuploidy breakpoints and somatic variation, while epigenetic remodeling there appears specific to cancer. The work defines somatic variation invisible to reference-based analyses.