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Transcriptomic profiles of myxofibrosarcoma and undifferentiated pleomorphic sarcoma correlate with clinical and genomic features

Mitra, Shamik LU ; Farswan, Akanksha ; Piccinelli, Paul LU ; Sydow, Saskia LU ; Hesla, Asle ; Tsagkozis, Panagiotis ; Vult von Steyern, Fredrik LU ; Almqvist, Martin ; Eriksson, Mikael LU orcid and Magnusson, Linda LU , et al. (2024) In Journal of Pathology 264(3). p.293-304
Abstract

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are two common and aggressive subtypes of soft tissue sarcoma. The aim of this study was to assess potential transcriptomic differences between MFS and UPS tumours and to evaluate the extent to which differences in gene expression profiles were associated with genomic and clinical features. The study included 162 patients with tumours diagnosed as MFS (N = 62) or UPS (N = 100). The patients had been diagnosed and treated at two Swedish sarcoma centres during a 30-year period. For gene expression profiling and gene fusion detection all tumours were analysed using RNA-sequencing and could be compared with data on clinical outcome (N = 155), global copy number profiles... (More)

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are two common and aggressive subtypes of soft tissue sarcoma. The aim of this study was to assess potential transcriptomic differences between MFS and UPS tumours and to evaluate the extent to which differences in gene expression profiles were associated with genomic and clinical features. The study included 162 patients with tumours diagnosed as MFS (N = 62) or UPS (N = 100). The patients had been diagnosed and treated at two Swedish sarcoma centres during a 30-year period. For gene expression profiling and gene fusion detection all tumours were analysed using RNA-sequencing and could be compared with data on clinical outcome (N = 155), global copy number profiles (N = 145), and gene mutations (N = 128). Gene expression profiling revealed three transcriptomic clusters (TCs) without any clear separation of MFS and UPS. One TC was associated with longer metastasis-free survival. These tumours had lower tumour mutation burden (TMB), were enriched for a copy number signature representative of focal LOH and chromosomal instability on a diploid background, and were relatively immune-depleted. MFS and UPS showed extensive genomic overlap, with whole genome doubling occurring more frequently among the latter. The results support the idea that MFS and UPS tumours have largely overlapping genomic and transcriptomic features, with UPS tumours showing more aggressive behaviour and more complex genomes. Independently of the tumour type, clinically relevant subgroups were revealed by gene expression analysis, and the finding of multiple genomic subgroups strongly suggest the existence of subgroups of relevance to treatment stratification.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
genomics, myxofibrosarcoma, outcome, transcriptomics, undifferentiated pleomorphic sarcoma
in
Journal of Pathology
volume
264
issue
3
pages
12 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:39258383
  • scopus:85203532195
ISSN
0022-3417
DOI
10.1002/path.6347
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
id
595debec-02cd-41bf-b889-68cbf6adcfe8
date added to LUP
2024-12-03 15:21:30
date last changed
2025-07-02 08:49:49
@article{595debec-02cd-41bf-b889-68cbf6adcfe8,
  abstract     = {{<p>Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are two common and aggressive subtypes of soft tissue sarcoma. The aim of this study was to assess potential transcriptomic differences between MFS and UPS tumours and to evaluate the extent to which differences in gene expression profiles were associated with genomic and clinical features. The study included 162 patients with tumours diagnosed as MFS (N = 62) or UPS (N = 100). The patients had been diagnosed and treated at two Swedish sarcoma centres during a 30-year period. For gene expression profiling and gene fusion detection all tumours were analysed using RNA-sequencing and could be compared with data on clinical outcome (N = 155), global copy number profiles (N = 145), and gene mutations (N = 128). Gene expression profiling revealed three transcriptomic clusters (TCs) without any clear separation of MFS and UPS. One TC was associated with longer metastasis-free survival. These tumours had lower tumour mutation burden (TMB), were enriched for a copy number signature representative of focal LOH and chromosomal instability on a diploid background, and were relatively immune-depleted. MFS and UPS showed extensive genomic overlap, with whole genome doubling occurring more frequently among the latter. The results support the idea that MFS and UPS tumours have largely overlapping genomic and transcriptomic features, with UPS tumours showing more aggressive behaviour and more complex genomes. Independently of the tumour type, clinically relevant subgroups were revealed by gene expression analysis, and the finding of multiple genomic subgroups strongly suggest the existence of subgroups of relevance to treatment stratification.</p>}},
  author       = {{Mitra, Shamik and Farswan, Akanksha and Piccinelli, Paul and Sydow, Saskia and Hesla, Asle and Tsagkozis, Panagiotis and Vult von Steyern, Fredrik and Almqvist, Martin and Eriksson, Mikael and Magnusson, Linda and Nilsson, Jenny and Pillay, Nischalan and Mertens, Fredrik}},
  issn         = {{0022-3417}},
  keywords     = {{genomics; myxofibrosarcoma; outcome; transcriptomics; undifferentiated pleomorphic sarcoma}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{293--304}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Journal of Pathology}},
  title        = {{Transcriptomic profiles of myxofibrosarcoma and undifferentiated pleomorphic sarcoma correlate with clinical and genomic features}},
  url          = {{http://dx.doi.org/10.1002/path.6347}},
  doi          = {{10.1002/path.6347}},
  volume       = {{264}},
  year         = {{2024}},
}