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Cited by 23Sarcoma Diagnosis and TreatmentCancer-related Molecular PathwaysChromatin Remodeling and Cancer

Normal and Functional TP53 in Genetically Stable Myxoid/Round Cell Liposarcoma

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Ståhlberg, Anders, Kåbjörn Gustafsson, Christina, Engtröm, Katarina, Thomsen, Christer, Dolatabadi, Soheila, Jonasson, Emma, Li, Chieh-Yuan, Ruff, David +2 more·2014·PLoS ONE
DOI 10.1371/journal.pone.0113110PMC PMC4231113
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Abstract

Myxoid/round-cell liposarcoma (MLS/RCLS) is characterized by either the fusion gene FUS-DDIT3 or the less commonly occurring EWSR1-DDIT3 and most cases carry few or no additional cytogenetic changes. There are conflicting reports concerning the status and role of TP53 in MLS/RCLS. Here we analysed four MLS/RCLS derived cell lines for TP53 mutations, expression and function. Three SV40 transformed cell lines expressed normal TP53 proteins. Irradiation caused normal posttranslational modifications of TP53 and induced P21 expression in two of these cell lines. Transfection experiments showed that the FUS-DDIT3 fusion protein had no effects on irradiation induced TP53 responses. Ion Torrent AmpliSeq screening, using the Cancer Hotspot panel, showed no dysfunctional or disease associated alleles/mutations. In conclusion, our results suggest that most MLS/RCLS cases carry functional TP53 genes and this is consistent with the low numbers of secondary mutations observed in this tumor entity.

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  • Deviance from a physiological trajectory might be intertwined with gestational complications such as hypertensive disorders of pregnancy, fetal growth restriction, and others.

    “While these modifications are pivotal to support fetal development, their deviance from a physiological trajectory might be intertwined with some gestational complications such as hypertensive disorders of pregnancy, fetal growth restriction and others [2-5].”

    From Trimester-Specific Bioelectrical Impedance Reference Curves in Physiological Pregnancy: Mapping Maternal Body Composition and Hydration Trajectories (2026) · cites this paper as [3]

    The Introduction and Results and Discussion address TP53 function and genetic stability in myxoid/round cell liposarcoma, not pregnancy. Searches for gestational complications, hypertensive disorders, fetal growth restriction, and physiological pregnancy changes found no passage addressing the claim. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • The remarkable stability of the TBW trajectory across different pre-pregnancy BMI strata suggests that gestational fluid expansion is a highly preserved, 'hardwired' evolutionary adaptation designed to support placental perfusion.

    “The remarkable stability of the TBW trajectory across different pre-pregnancy BMI strata suggested that gestational fluid expansion is a highly preserved, 'hardwired' evolutionary adaptation designed to support placental perfusion [1-3].”

    From Trimester-Specific Bioelectrical Impedance Reference Curves in Physiological Pregnancy: Mapping Maternal Body Composition and Hydration Trajectories (2026) · cites this paper as [3]

    The Results and Discussion passages concern TP53 expression and genetic stability in myxoid/round cell liposarcoma. Searches for TBW trajectories, pre-pregnancy BMI, gestational fluid expansion, and placental perfusion found no passage addressing the claim. The cited paper therefore cannot verify this part of the sentence. (LLM, conf=0.79)

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References 35 · Cited by 23

Research works printed but not linked: 35

  1. [1]Mertens F, Panagopoulos I, Mandahl N (2010) Genomic characteristics of soft tissue sarcomas. Virchows Arch 456: 129– 139. 19189124
  2. [2]Aman P (1999) Fusion genes in solid tumors. Semin Cancer Biol 9: 303– 318. 10448117
  3. [3]Åman P, Ron D, Mandahl N, Fioretos T, Heim S, et al (1992) Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11). Genes Chromosom Cancer 5: 278– 285. 1283316
  4. [4]Panagopoulos I, Höglund M, Mertens F, Mandahl N, Mitelman F, et al (1996) Fusion of the EWS and CHOP genes in myxoid liposarcoma. Oncogene 12: 489– 494. 8637704
  5. [5]Engström K, Willén H, Kåbjörn-Gustafsson C, Andersson C, Olsson M, et al (2006) The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells. Am J Pathol 168: 1642– 1653. 16651630 PMC1606602
  6. [6]Sanchez Garcia I, Rabbitts TH (1994) Transcriptional activation by TAL1 and FUS-CHOP proteins expressed in acute malignancies as a result of chromosomal abnormalities. Proc Natl Acad Sci U S A 91: 7869– 7873. 8058726 PMC44505
  7. [7]Zinszner H, Albalat R, Ron D (1994) A novel effector domain from the RNA-binding protein TLS or EWS is required for oncogenic transformation by CHOP. Genes Dev 8: 2513– 2526. 7958914
  8. [8]Zinszner H, Immanuel D, Yin Y, Liang FX, Ron D (1997) A topogenic role for the oncogenic N-terminus of TLS: nucleolar localization when transcription is inhibited. Oncogene 14: 451– 461. 9053842
  9. [9]Di Giandomenico S, Frapolli R, Bello E, Uboldi S, Licandro SA, et al (2013) Mode of action of trabectedin in myxoid liposarcomas. Oncogene doi: 10-1038/onc.2013.462 24213580
  10. [10]Forni C, Minuzzo M, Virdis E, Tamborini E, Simone M, et al (2009) Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors. Mol Cancer Ther 8: 449– 457. 19190116
  11. [11]Frapolli R, Tamborini E, Virdis E, Bello E, Tarantino E, et al (2010) Novel models of myxoid liposarcoma xenografts mimicking the biological and pharmacologic features of human tumors. Clin Cancer Res 16: 4958– 4967. 20732964
  12. [12]Barretina J, Taylor BS, Banerji S, Ramos AH, Lagos-Quintana M, et al (2010) Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nature Genet 42: 715– 721. 20601955 PMC2911503
  13. [13]Pilotti S, Lavarino C, Mezzelani A, Della Torre C, Minoletti F, et al (1998) Limited role of TP53 and TP53-related genes in myxoid liposarcoma. Tumori 84: 571– 577. 9862519
  14. [14]Mandahl N, Mertens F, Aman P, Rydholm A, Brosjo O, et al (1994) Nonrandom secondary chromosome-aberrations in liposarcomas with t(12, 16). Int J Oncol 4: 307– 310. 21566924
  15. [15]Antonescu CR, Tschernyavsky SJ, Decuseara R, Leung DH, Woodruff JM, et al (2001) Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases. Clin Cancer Res 7: 3977– 3987. 11751490
  16. [16]Oda Y, Yamamoto H, Takahira T, Kobayashi C, Kawaquchi K, et al (2005) Frequent alteration of p16(INK4a)/p14(ARF) and p53 pathways in the round cell component of myxoid/round cell liposarcoma: p53 gene alterations and reduced p14(ARF) expression both correlate with poor prognosis. J Pathol 207: 410– 421. 16177957
  17. [17]Perrone F, Tamborini E, Suardi S, Lagonigro MS, Pilotti S (2006) Re: Oda et al. Frequent alteration of p16INK4a/p14ARF and p53 pathways in the round cell component of myxoid/round cell liposarcoma: p53 gene alterations and reduced p14ARF expression both correlate with poor prognosis. J Pathol 2005;207: 410– 421 J Pathol 209: 281; author reply 282. 16622896
  18. [18]Engström K, Bergh P, Cederlund CG, Hultborn R, Willen H, et al (2007) Irradiation of myxoid/round cell liposarcoma induces volume reduction and lipoma-like morphology. Acta Oncol 46: 838– 845. 17653909
  19. [19]Rodriguez R, Rubio R, Gutierrez-Aranda I, Melen GJ, Elosua C, et al (2011) FUS-CHOP fusion protein expression coupled to p53 deficiency induces liposarcoma in mouse but not in human adipose-derived mesenchymal stem/stromal cells. Stem Cells 29: 179– 192. 21732477
  20. [20]Thomsen C, Grundevik P, Elias P, Ståhlberg A, Åman P (2013) A conserved N-terminal motif is required for complex formation between FUS, EWSR1, TAF15 and their oncogenic fusion proteins. FASEB J 27: 4965– 4974. 23975937
  21. [21]Göransson M, Elias E, Ståhlberg A, Olofsson A, Andersson C, et al (2005) Myxoid liposarcoma FUS-DDIT3 fusion oncogene induces C/EBP beta-mediated interleukin 6 expression. Int J Cancer 115: 556– 560. 15688424
  22. [22]Würl P, Taubert H, Meye A, Berger D, Lautenschläger C, et al (1997) Prognostic value of immunohistochemistry for p53 in primary soft-tissue sarcomas: a multivariate analysis of five antibodies. J Cancer Res Clin Oncol 123: 502– 508. 9341900 PMC12201079
  23. [23]Classon M, Henriksson M, Sumegi J, Klein G, Hammarskjold ML (1987) Elevated c-myc expression facilitates the replication of SV40 DNA in human lymphoma cells. Nature 330: 272– 274. 2823151
  24. [24]Thelin-Jarnum S, Lassen C, Panagopoulos I, Mandahl N, Åman P (1999) Identification of genes differentially expressed in TLS-CHOP carrying myxoid liposarcomas. Int J Cancer 83: 30– 33. 10449603
  25. [25]Pipas JM, Levine AJ (2001) Role of T antigen interactions with p53 in tumorigenesis. Semin Cancer Biol 11: 23– 30. 11243896
  26. [26]Technau A, Wolff A, Sauder C, Birkner N, Brandner G (2001) p53 in SV40-transformed DNA-damaged human cells binds to its cognate sequence but fails to transactivate target genes. Int J Oncol 18: 281– 286. 11172593
  27. [27]Sharma S, Schwarte-Waldhoff I, Oberhuber H, Schafer R (1993) Functional interaction of wild-type and mutant p53 transfected into human tumor cell lines carrying activated ras genes. Cell Growth Differ 4: 861– 869. 8274455
  28. [28]Khoury MP, Bourdon JC (2010) The isoforms of the p53 protein. Cold Spring Harb Perspect Biol 2: a000927. 20300206 PMC2829963
  29. [29]Andersson MK, Ståhlberg A, Arvidsson Y, Olofsson A, Semb H, et al (2008) The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response. BMC Cell Biol 9: 37. 18620564 PMC2478660
  30. [30]Law WJ, Cann KL, Hicks GG (2006) TLS, EWS and TAF15: a model for transcriptional integration of gene expression. Brief Funct Genomic Proteomic 5: 8– 14. 16769671
  31. [31]Fujii R, Takumi T (2005) TLS facilitates transport of mRNA encoding an actin-stabilizing protein to dendritic spines. J Cell Sci 118: 5755– 5765. 16317045
  32. [32]Gu B, Zhu WG (2012) Surf the post-translational modification network of p53 regulation. Int J Biol Sci 8: 672– 684. 22606048 PMC3354625
  33. [33]Hollstein M, Hainaut P (2010) Massively regulated genes: the example of TP53. J Pathol 220: 164– 173. 19918835
  34. [34]Wu L, Levine AJ (1997) Differential regulation of the p21/WAF-1 and mdm2 genes after high-dose UV irradiation: p53-dependent and p53-independent regulation of the mdm2 gene. Mol Med 3: 441– 451. 9260156 PMC2230214
  35. [35]Chin PL, Momand J, Pfeifer GP (1997) In vivo evidence for binding of p53 to consensus binding sites in the p21 and GADD45 genes in response to ionizing radiation. Oncogene 15: 87– 99. 9233781

Authors
Ståhlberg, A., Kåbjörn Gustafsson, C., Engtröm, K., Thomsen, C., Dolatabadi, S., Jonasson, E., Li, C.-Y., Ruff, D., Chen, S.-M., & Åman, P.
Affiliations
  • University of Gothenburg (SE)
  • Thermo Fisher Scientific (United States) (US)
Corresponding author
Åman, Pierre
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-11-13
Volume
9
Issue
11
Pages
e113110
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0113110
PMC
PMC4231113
OpenAlex
W2079386541
Cited by
23
References
35
Citations by year
2026: 1 · 2025: 1 · 2024: 4 · 2023: 3 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2
FWCI
1.60
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Cancerfonden
  • Stiftelserna Wilhelm och Martina Lundgrens
  • Svenska Sällskapet för Medicinsk Forskning
  • Vetenskapsrådet
  • Göteborgs Universitet
  • Johan Jansson Foundation
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
myxoid liposarcoma, TP53, TP53 mutation, p21 expression, secondary mutations
MeSH terms
Cell Line, Transformed, Humans, Mutation, Tumor Suppressor Protein p53, Liposarcoma, Myxoid, Genomic Instability, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21

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