Specificity of TLS-CHOP rearrangement for classic myxoid/round cell liposarcoma: Absence in predominantly myxoid well-differentiated liposarcomas Journal Article

Authors: Antonescu, C. R.; Elahi, A.; Humphrey, M.; Lui, M. Y.; Healey, J. H.; Brennan, M. F.; Woodruff, J. M.; Jhanwar, S. C.; Ladanyi, M.
Article Title: Specificity of TLS-CHOP rearrangement for classic myxoid/round cell liposarcoma: Absence in predominantly myxoid well-differentiated liposarcomas
Abstract: Myxoid liposarcoma (LS), the most common subtype of LS, is known to be characterized by the specific t(12;16) resulting in a TLS-CHOP fusion in almost all cases. We wished to address the following questions: (i) Is this genetic hallmark also present in other types of LS with predominant myxoid change? (ii) What is the proportion of cases with the variant EWS-CHOP fusion? (iii) What is the optimal approach for Southern blot detection of TLS breakpoints? We identified 59 LS characterized histologically by >90% myxoid component, in which frozen tissue tumor was available for DNA extraction. These 59 LS with myxoid features were divided into 2 groups: 42 LS with classic myxoid/round cell appearance (myxoid LS) and 17 well-differentiated LS (WDLS) with a predominant (>90%) myxoid component. Within the myxoid LS group, 29 tumors were low grade and 13 high grade (>20% round cell component). Among the 17 predominantly myxoid WDLS, there were 15 low grade and 2 focally high grade tumors. In addition, we selected as control group, 20 LS of other histological types with minimal or no myxoid change (17 WDLS and 3 pleomorphic LS) and 13 myxofibrosarcomas. Southern blot analysis was performed in all cases using a CHOP cDNA probe, and in all CHOP rearranged cases using a TLS cDNA probe. Probe/enzyme combinations for Southern blot analysis were CHOP exon 3-4 cDNA probe with BamHI or SacI, TLS exon 3-6 cDNA probe with BclI. All 42 cases of myxoid LS showed a CHOP rearrangement and 38 of them also had a TLS rearrangement. Among the 4 myxoid LS without Southern blot evidence of TLS rearrangement, 1 showed an EWS-CHOP fusion by Southern blotting and reverse transcriptase-polymerase chain reaction and in another case, reverse transcriptase-polymerase chain reaction detected a TLS-CHOP fusion transcript. None of the predominantly myxoid WDLS and none of the tumors included in the control group showed rearranegements with CHOP probe. In addition, 12 predominantly myxoid WDLS, 10 other LS, and 5 myxofibrosarcoma from the control group were also tested for TLS rearrangement; all were negative. The TLS-CHOP fusion is highly sensitive and specific for the entity of classic myxoid/round cell LS. Other types of LS, even with a predominant myxoid component, lack the TLS-CHOP rearrangement, confirming that they represent a genetically distinct group of LS. The prevalence of the EWS-CHOP variant fusion was approximately 2% in this series. The optimal enzyme for TLS genomic breakpoint detection is BclI. Copyright © American Society for Investigative Pathology and the Association for Molecular Pathology.
Keywords: oncoprotein; gene translocation; genetics; classification; rna binding protein; oncogene proteins, fusion; ribonucleoproteins; chromosome breakage; translocation, genetic; fibroma; rna binding protein ews; cytochemistry; histocytochemistry; ccaat-enhancer-binding proteins; chromosome map; chromosome mapping; small cell carcinoma; myxosarcoma; carcinoma, small cell; rna-binding protein ews; southern blotting; rna-binding protein fus; growth arrest and dna damage inducible protein 153; ribonucleoprotein; liposarcoma, myxoid; transcription factor chop; ccaat enhancer binding protein; blotting, southern; heterogeneous nuclear ribonucleoprotein; heterogeneous-nuclear ribonucleoproteins; humans; human; article; tls chop fusion protein, human; tls-chop fusion protein, human
Journal Title: Journal of Molecular Diagnostics
Volume: 2
Issue: 3
ISSN: 1525-1578
Publisher: Elsevier Science, Inc.  
Date Published: 2000-08-01
Start Page: 132
End Page: 138
Language: English
PUBMED: 11229517
PROVIDER: scopus
PMCID: PMC1906905
DOI: 10.1016/S1525-1578(10)60628-9
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Abul H F Elahi
    15 Elahi
  2. Murray F Brennan
    756 Brennan
  3. Cristina R Antonescu
    606 Antonescu
  4. Marc Ladanyi
    862 Ladanyi
  5. Suresh C Jhanwar
    207 Jhanwar
  6. John H Healey
    374 Healey
  7. James M Woodruff
    128 Woodruff
  8. Man Yee Lui
    18 Lui