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

A near-telomere-to-telomere assembly reveals that 16% of somatic variants in melanoma occur in sequences absent from the reference genome, highlighting previously inaccessible genomic regions.

• Why it matters: Understanding the full landscape of somatic variation is crucial for insights into cancer development and progression, but many genomic regions remain uncharacterized with conventional methods.
• What they did: Researchers combined a near-T2T diploid assembly with deep short- and long-read sequencing of melanoma samples, identifying somatic variants in novel sequences, and analyzing centromere and telomere dynamics.
• The result: Findings show satellite repeats as UV mutagenesis hotspots, centromere domains as sites of genetic variation and aneuploidy, and widespread somatic epimutations, providing a new framework for studying human mosaicism.