Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing


Cortés-Ciriano I, Lee JJ-K, Xi R, Jain D, Jung YL, Yang L, Gordenin D, Klimczak LJ, Zhang C-Z, Pellman DS, PCAWG Structural Variation Working Group (incl. Lee EA), Park PJ, PCAWG-Consortium. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing. Nat Genet 2020;52(3):331-341.

Date Published:

2020 03


Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.

Last updated on 06/12/2020