Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development

By P. Stephens, C. Greenman, B. Fu, Fengtang Yang, G. Bignell, L. Mudie, E. Pleasance, K. Lau, D. Beare, L. Stebbings and 22 more. Cell, 2011

2,355 citations recorded by the source corpus.

Summary Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%–3% of all cancers, across many subtypes, and is present in ∼25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. PaperClip

Subfields: Cancer Research, Genetics, Plant Science

View Paper: https://www.semanticscholar.org/paper/e2f0d30d1790a201c4bc967591cab7ba7fe8af5f

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Citations in the corpus

Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients (2018, background): “In analogy to the term chromothripsis (Stephens et al., 2011), we call this effect syndeo mechanism thripsis, or syndeothripsis.”
Genomic Evolution of Breast Cancer Metastasis and Relapse (2017, background): “These included an event that generated a complex amplification of CCND1 coupled with loss of one copy of TP53 (Figure 4A) and a chromothripsis (Stephens et al., 2011) event that resulted in FGFR1 amplification (Figure 4B).”
The genetic basis of early T-cell precursor acute lymphoblastic leukaemia (2012, background): “Three cases (SJTALL001, SJTALL002, SJTALL003) had multiple complex rearrangements with breakpoints suggestive of a single cellular catastrophe (“chromothripsis&rdquo”
The Life History of 21 Breast Cancers (2012, neutral): “This pattern is different to mechanisms of genomic amplification such as breakage-fusion-bridge or double minute chromosomes, where amplification can occur rapidly and even exponentially over a few cell cycles (Bignell et al., 2007; Campbell et al., 2010; Stephens et al., 2011).”
Catastrophic nuclear envelope collapse in cancer cell micronuclei (2013, background): “These chromatin pieces are hypothesized to be source material for the massive single-chromosome rearrangement process termed chromothripsis (Crasta et al., 2012), which occurs in a wide variety of cancers (Stephens et al., 2011).”
Whole genomes redefine the mutational landscape of pancreatic cancer (2015, background): “The majority of structural variants were intra-chromosomal (10,114) and were classified into 7 types: intra-chromosomal rearrangements (5,860), deletions (1,393), duplications (128), tandem duplications (179), inversions (1,629), foldback inversions (579) and amplified inversions (346); inter-chromo”