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Scattered genomic amplification in dedifferentiated liposarcoma

Mandahl, Nils LU ; Magnusson, Linda LU ; Nilsson, Jenny LU ; Viklund, Björn; Arbajian, Elsa LU ; Von Steyern, Fredrik Vult LU ; Isaksson, Anders and Mertens, Fredrik LU (2017) In Molecular Cytogenetics 10(1).
Abstract

Background: Atypical lipomatous tumor (ALT), well differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS) are cytogenetically characterized by near-diploid karyotypes with no or few other aberrations than supernumerary ring or giant marker chromosomes, although DDLS tend to have somewhat more complex rearrangements. In contrast, pleomorphic liposarcomas (PLS) have highly aberrant and heterogeneous karyotypes. The ring and giant marker chromosomes contain discontinuous amplicons, in particular including multiple copies of the target genes CDK4, HMGA2 and MDM2 from 12q, but often also sequences from other chromosomes. Results: The present study presents a DDLS with an atypical hypertriploid karyotype without any ring or... (More)

Background: Atypical lipomatous tumor (ALT), well differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS) are cytogenetically characterized by near-diploid karyotypes with no or few other aberrations than supernumerary ring or giant marker chromosomes, although DDLS tend to have somewhat more complex rearrangements. In contrast, pleomorphic liposarcomas (PLS) have highly aberrant and heterogeneous karyotypes. The ring and giant marker chromosomes contain discontinuous amplicons, in particular including multiple copies of the target genes CDK4, HMGA2 and MDM2 from 12q, but often also sequences from other chromosomes. Results: The present study presents a DDLS with an atypical hypertriploid karyotype without any ring or giant marker chromosomes. SNP array analyses revealed amplification of almost the entire 5p and discontinuous amplicons of 12q including the classical target genes, in particular CDK4. In addition, amplicons from 1q, 3q, 7p, 9p, 11q and 20q, covering from 2 to 14 Mb, were present. FISH analyses showed that sequences from 5p and 12q were scattered, separately or together, over more than 10 chromosomes of varying size. At RNA sequencing, significantly elevated expression, compared to myxoid liposarcomas, was seen for TRIO and AMACR in 5p and of CDK4, HMGA2 and MDM2 in 12q. Conclusions: The observed pattern of scattered amplification does not show the characteristics of chromothripsis, but is novel and differs from the well known cytogenetic manifestations of amplification, i.e., double minutes, homogeneously staining regions and ring chromosomes. Possible explanations for this unusual distribution of amplified sequences might be the mechanism of alternative lengthening of telomeres that is frequently active in DDLS and events associated with telomere crisis.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
12q, 5p, Amplification, Chromosomes, Gene expression, Liposarcoma
in
Molecular Cytogenetics
volume
10
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85021247590
  • wos:000404100100001
ISSN
1755-8166
DOI
10.1186/s13039-017-0325-5
language
English
LU publication?
yes
id
df7ac00b-fbca-4eee-b027-e1b728b20c98
date added to LUP
2017-08-10 11:57:07
date last changed
2017-09-18 11:41:17
@article{df7ac00b-fbca-4eee-b027-e1b728b20c98,
  abstract     = {<p>Background: Atypical lipomatous tumor (ALT), well differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS) are cytogenetically characterized by near-diploid karyotypes with no or few other aberrations than supernumerary ring or giant marker chromosomes, although DDLS tend to have somewhat more complex rearrangements. In contrast, pleomorphic liposarcomas (PLS) have highly aberrant and heterogeneous karyotypes. The ring and giant marker chromosomes contain discontinuous amplicons, in particular including multiple copies of the target genes CDK4, HMGA2 and MDM2 from 12q, but often also sequences from other chromosomes. Results: The present study presents a DDLS with an atypical hypertriploid karyotype without any ring or giant marker chromosomes. SNP array analyses revealed amplification of almost the entire 5p and discontinuous amplicons of 12q including the classical target genes, in particular CDK4. In addition, amplicons from 1q, 3q, 7p, 9p, 11q and 20q, covering from 2 to 14 Mb, were present. FISH analyses showed that sequences from 5p and 12q were scattered, separately or together, over more than 10 chromosomes of varying size. At RNA sequencing, significantly elevated expression, compared to myxoid liposarcomas, was seen for TRIO and AMACR in 5p and of CDK4, HMGA2 and MDM2 in 12q. Conclusions: The observed pattern of scattered amplification does not show the characteristics of chromothripsis, but is novel and differs from the well known cytogenetic manifestations of amplification, i.e., double minutes, homogeneously staining regions and ring chromosomes. Possible explanations for this unusual distribution of amplified sequences might be the mechanism of alternative lengthening of telomeres that is frequently active in DDLS and events associated with telomere crisis.</p>},
  articleno    = {25},
  author       = {Mandahl, Nils and Magnusson, Linda and Nilsson, Jenny and Viklund, Björn and Arbajian, Elsa and Von Steyern, Fredrik Vult and Isaksson, Anders and Mertens, Fredrik},
  issn         = {1755-8166},
  keyword      = {12q,5p,Amplification,Chromosomes,Gene expression,Liposarcoma},
  language     = {eng},
  month        = {06},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Molecular Cytogenetics},
  title        = {Scattered genomic amplification in dedifferentiated liposarcoma},
  url          = {http://dx.doi.org/10.1186/s13039-017-0325-5},
  volume       = {10},
  year         = {2017},
}