The Architecture and Evolution of Cancer Neochromosomes
Open accessAbstract
We isolated and analyzed, at single-nucleotide resolution, cancer-associated neochromosomes from well- and/or dedifferentiated liposarcomas. Neochromosomes, which can exceed 600 Mb in size, initially arise as circular structures following chromothripsis involving chromosome 12. The core of the neochromosome is amplified, rearranged, and corroded through hundreds of breakage-fusion-bridge cycles. Under selective pressure, amplified oncogenes are overexpressed, while coamplified passenger genes may be silenced epigenetically. New material may be captured during punctuated chromothriptic events. Centromeric corrosion leads to crisis, which is resolved through neocentromere formation or native centromere capture. Finally, amplification terminates, and the neochromosome core is stabilized in linear form by telomere capture. This study investigates the dynamic mutational processes underlying the life history of a special form of cancer mutation.
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The MDM2 boundary effects in leiomyosarcoma are likely due to neochromosome formations that included the MDM2 and CDK4 genes.
“In addition, boundaries near the MDM2 locus were most affected in leiomyosarcoma (Fig. 3b), likely due to neochromosome formations that included the MDM2 and CDK4 genes31.”
From Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer (2020) · cites this paper as [31]
Boundaries near the MDM2 locus were most affected in leiomyosarcoma.
“In addition, boundaries near the MDM2 locus were most affected in leiomyosarcoma (Fig. 3b), likely due to neochromosome formations that included the MDM2 and CDK4 genes31.”
From Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer (2020) · cites this paper as [31]
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- Authors
- Garsed, D. W., Marshall, O. J., Corbin, V. D. A., Hsu, A., Di Stefano, L., Schröder, J., Li, J., Feng, Z.-P., Kim, B. W., Kowarsky, M., Lansdell, B., Brookwell, R., Myklebost, O., Meza-Zepeda, L., Holloway, A. J., Pedeutour, F., Choo, K. H. A., Damore, M. A., Deans, A. J., Papenfuss, A. T., & Thomas, D. M.
- Affiliations
- The University of Melbourne (AU)
- Royal Children's Hospital (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Peter MacCallum Cancer Centre (AU)
- Sullivan Nicolaides Pathology (AU)
- Oslo University Hospital (NO)
- Amgen (United States) (US)
- Garvan Institute of Medical Research (AU)
- Corresponding author
- Papenfuss, Anthony T.
- Thomas, David M.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 26
- Issue
- 5
- Pages
- 653-667
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W1986820103
- Cited by
- 194
- References
- 45
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 16 · 2023: 11 · 2022: 19 · 2021: 23 · 2020: 27 · 2019: 20 · 2018: 19 · 2017: 21 · 2016: 14 · 2015: 10 · 2014: 2
- FWCI
- 10.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Figshare (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- liposarcoma, chromothripsis, chromosome 12, breakage-fusion-bridge cycles, oncogene amplification, epigenetic silencing, passenger genes, chromosomal instability, tumor evolution
- MeSH terms
- Aged, Centromere, Chromosome Aberrations, Chromosomes, Human, Female, Humans, Liposarcoma, Models, Genetic, Oncogenes, Retroperitoneal Neoplasms, Translocation, Genetic, Mutagenesis, Cell Line, Tumor, Carcinogenesis
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