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MDM2 amplification in rod-shaped chromosomes provides clues to early stages of circularized gene amplification in liposarcoma

Sydow, Saskia LU ; Piccinelli, Paul LU ; Mitra, Shamik LU ; Tsagkozis, Panagiotis ; Hesla, Asle ; B. R. De Mattos, Camila ; Köster, Jan LU ; Magnusson, Linda LU ; Nilsson, Jenny LU and Ameur, Adam , et al. (2024) In Communications Biology 7(1).
Abstract

Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this hypothesis, we compared WDLSs with Chr12 amplification in rod-shaped chromosomes with WDLSs with rings. Both types of amplicons share the same spectrum of structural variants (SVs), show higher SV frequencies in Chr12 than in co-amplified segments, have SVs that fuse the telomeric ends of co-amplified chromosomes, and lack interspersed deletions. Combined with the finding of cells with transient rod-shaped structures in tumors with ring... (More)

Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this hypothesis, we compared WDLSs with Chr12 amplification in rod-shaped chromosomes with WDLSs with rings. Both types of amplicons share the same spectrum of structural variants (SVs), show higher SV frequencies in Chr12 than in co-amplified segments, have SVs that fuse the telomeric ends of co-amplified chromosomes, and lack interspersed deletions. Combined with the finding of cells with transient rod-shaped structures in tumors with ring chromosomes, this suggests a stepwise process starting with the gain of Chr12 material that, after remodeling which does not fit with classical chromothripsis, forms a dicentric structure with other chromosomes. Depending on if and when telomeres from other chromosomes are captured, circularized or linear gain of 12q sequences will predominate.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Communications Biology
volume
7
issue
1
article number
606
publisher
Nature Publishing Group
external identifiers
  • scopus:85193712817
  • pmid:38769442
ISSN
2399-3642
DOI
10.1038/s42003-024-06307-1
language
English
LU publication?
yes
id
41c1cc94-9484-4568-bb42-439b08c18f5b
date added to LUP
2024-06-04 14:57:10
date last changed
2024-06-18 15:42:02
@article{41c1cc94-9484-4568-bb42-439b08c18f5b,
  abstract     = {{<p>Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this hypothesis, we compared WDLSs with Chr12 amplification in rod-shaped chromosomes with WDLSs with rings. Both types of amplicons share the same spectrum of structural variants (SVs), show higher SV frequencies in Chr12 than in co-amplified segments, have SVs that fuse the telomeric ends of co-amplified chromosomes, and lack interspersed deletions. Combined with the finding of cells with transient rod-shaped structures in tumors with ring chromosomes, this suggests a stepwise process starting with the gain of Chr12 material that, after remodeling which does not fit with classical chromothripsis, forms a dicentric structure with other chromosomes. Depending on if and when telomeres from other chromosomes are captured, circularized or linear gain of 12q sequences will predominate.</p>}},
  author       = {{Sydow, Saskia and Piccinelli, Paul and Mitra, Shamik and Tsagkozis, Panagiotis and Hesla, Asle and B. R. De Mattos, Camila and Köster, Jan and Magnusson, Linda and Nilsson, Jenny and Ameur, Adam and Wardenaar, René and Foijer, Floris and Spierings, Diana and Mertens, Fredrik}},
  issn         = {{2399-3642}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Communications Biology}},
  title        = {{MDM2 amplification in rod-shaped chromosomes provides clues to early stages of circularized gene amplification in liposarcoma}},
  url          = {{http://dx.doi.org/10.1038/s42003-024-06307-1}},
  doi          = {{10.1038/s42003-024-06307-1}},
  volume       = {{7}},
  year         = {{2024}},
}