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Cited by 204Cancer Genomics and DiagnosticsGenomic variations and chromosomal abnormalitiesGenome Rearrangement Algorithms

Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer

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Kloosterman, Wigard P, Hoogstraat, Marlous, Paling, Oscar, Tavakoli-Yaraki, Masoumeh, Renkens, Ivo, Vermaat, Joost S, van Roosmalen, Markus J, van Lieshout, Stef +8 more·2011·Genome Biology
DOI 10.1186/gb-2011-12-10-r103PMC PMC3333773
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Abstract

Background: Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear. Results: We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner. Conclusions: We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis.

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  • Topological evolutionary genomics approaches can be used in chromosomal instabilities in cancer, through mechanisms like chromothripsis.

    “Finally, topological evolutionary genomics approaches can also be used in much faster but configurationally important processes, such as chromosomal instabilities in cancer, through mechanisms like chromothripsis (204) ( Figure 6 ).”

    From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [204]

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Authors
Kloosterman, W. P., Hoogstraat, M., Paling, O., Tavakoli-Yaraki, M., Renkens, I., Vermaat, J. S., van Roosmalen, M. J., van Lieshout, S., Nijman, I. J., Roessingh, W., van 't Slot, R., van de Belt, J., Guryev, V., Koudijs, M., Voest, E., & Cuppen, E.
Affiliations
University Medical Center Utrecht (NL)
Corresponding author
Cuppen, Edwin
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2011-10-19
Volume
12
Issue
10
Pages
R103-R103
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/gb-2011-12-10-r103
PMC
PMC3333773
OpenAlex
W2133744934
Cited by
204
References
3
Citations by year
2026: 4 · 2025: 5 · 2024: 10 · 2023: 11 · 2022: 10 · 2021: 10 · 2020: 10 · 2019: 6 · 2018: 11 · 2017: 16 · 2016: 19 · 2015: 16 · 2014: 22 · 2013: 31 · 2012: 21
FWCI
8.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion, cc-by)
  • Socio-Environmental Systems Modeling (acceptedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
  • KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
Keywords
chromothripsis, colorectal cancer, metastatic colorectal cancer, structural rearrangement, somatic structural variants, chromosome shattering, Notch2, EXO1, MLL3, somatic mutations, APC, KRAS, SMAD4, PIK3CA, copy number alterations, carcinogenesis
MeSH terms
Chromosome Aberrations, Chromosomes, Human, DNA-Binding Proteins, DNA, Neoplasm, Exodeoxyribonucleases, Female, Gene Frequency, Humans, Liver Neoplasms, Male, Colorectal Neoplasms, Gene Rearrangement, Case-Control Studies, Point Mutation, Gene Dosage, Computational Biology, Polymorphism, Single Nucleotide, DNA Repair Enzymes, Receptor, Notch2, Genes, Neoplasm

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