Alterations in the structure and location of telomeres are pivotal in cancer genome evolution. Here, we applied both long-read and short-read genome sequencing to assess telomere repeat-containing structures in cancers and cancer cell lines. Using long-read genome sequences that span telomeric repeats, we defined four types of telomere repeat variations in cancer cells: neotelomeres where telomere addition heals chromosome breaks, chromosomal arm fusions spanning telomere repeats, fusions of neotelomeres, and peri-centromeric fusions with adjoined telomere and centromere repeats. These results provide a framework for the systematic study of telomeric repeats in cancer genomes, which could serve as a model for understanding the somatic evolution of other repetitive genomic elements.
Long-read cancer DNA sequences define structure of neotelomeres and telomere fusions
Neotelomeres have similar telomere length as normal chromosomal arms
Short telomeric repeats are found at sites of chromosomal arm fusions
Frequency of neotelomere and arm fusion events varies across 40 cancer types
Long-read genome sequencing describes the existence and structures of neotelomeres and telomere-spanning chromosome arm fusions in cancer samples. Short-read sequences of 3,651 cancer samples were used to infer the frequency of these telomeric alterations across 40 cancer types.