Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Soft tissue tumors: Liposarcoma / malignant lipomatous tumors


Phylum Soft Tissue Tumors:Liposarcoma
Note liposarcomas are adipose tissue tumors, including low-malignant to highly malignant subtypes, constituting 10-15% of soft tissue sarcomas


  • Well-differentiated liposarcoma: the well-differentiated liposarcomas are tumors of low grade malignancy that may recur locally but not metastasize; the terminolgy of subtypes is not straightforward; three related sybtypes have been distinguished: lipoma-like (the most common form), inflammatory, and sclerosing; other terms that have been suggested to describe at least subsets of these tumors are atypical lipoma and atypical lipomatous tumor
  • Myxoid liposarcoma / round cell liposarcoma: myxoid liposarcoma is the most common form of liposarcomas, constituting about half of the cases, with a relatively favorable prognosis; the much less common, and more aggressive round cell liposarcoma is regarded as a poorly differentiated variant of myxoid liposarcoma; pure round cell liposarcomas are very rare, and more often the tumors represent mixed liposarcomas with both myxoid and round cell components at different proportions; in recurrences the round cell component may increase
  • Pleomorphic liposarcoma: the pleomorphic liposarcomas are highly malignant tumors showing a disorderly growth pattern and extensive cellular pleomorphism
  • Clinics and Pathology

    Epidemiology the reported annual incidence of liposarcoma is in the range of 2.5 per million; liposarcomas are tumors of adult life with a median age of 55-60 years; patients younger than 15 years are rare; men are slightly more often affected than women
    Clinics the major sites are the lower extremities and the retroperitoneum; most tumors range from 5 to 10 cm in diameter, but much larger tumors are not rarely seen.
    Evolution the risk of distant metastases relate to the type and degree of histological differentiation; well-differentiated liposarcomas may occasionally dedifferentiate to highly malignant tumors that may metastasize
    Prognosis the survival rates are primarily dependent on the histological type, and patients with well-differentiated and myxoid liposarcomas, on the one hand, fare much better than round cell and pleomorphic liposarcomas on the other hand


    Well-differentiated liposarcoma / atypical lipomatous tumor
  • the vast majority of this subset of tumors, irrespective of whether classified as atypical lipomatous tumor, atypical lipoma, or well-differentiated liposarcoma, is characterized by the presence of one or more supernumerary ring chromosome or giant marker chromosome
  • frequently, these show an extensive intratumor variability in size and number; this has been attributed to mitotic irregularities due to breakage-fusion-bridge cycles, which are also associated with the observed nuclear atypia
  • in about one-third of the cases, there are, in addition to rings and markers, a few other numerical and/or structural aberrations; these changes do not show any obvious non-random pattern, with the exception of loss of 13q material
  • another characteristic feature, seen in the majority of these tumors, is the high frequency of telomeric associations, showing a non-random pattern with a preferential involvement of the 11p telomere
  • some tumors with minimal atypia have been reported to show gain of 12q15-q24 sequences rather than rings and markers or balanced translocations of 12q13-15, which is a typical feature of benign, ordinary lipomas
  • Cytogenetics Molecular
  • the ring and giant marker chromosomes have been shown to contain regularly material from 12q and, occasionally, material from another chromosome that may vary from case to case, except for the frequent occurrence of amplified sequences from 1q21 in inter-/intramuscular tumors
  • several tumor-associated genes, localized to 12q13-q21, are amplified; these include in particular MDM2, but also SAS, CDK4, and HMGIC; the size of the amplicon vary, and two or more of these genes as well as other sequences may be co-amplified, although frequently at different levels; with few exceptions, MDM2 is not only amplified but also overexpressed
  • most rings are negative for chromosome specific centromere probes by FISH, but have centromeric activity as indicated by the positivity for anti CENP-C antibodies

  • Cytogenetics
    Myxoid liposarcoma / round cell liposarcoma:
  • the specific rearrangement t(12;16)(q13;p11), or variants involving one or more additional chromosomes in complex translocations, is found in about 90% of myxoid liposarcomas, including tumors with a mixture of myxoid and round cell components; in one-third of the cases this translocation is the sole cytogenetic anomaly; the most common secondary aberration, seen in 6-7% of the cases, is trisomy 8
  • the alternative t(12;22)(q13;q12), most often seen in seemingly unbalanced or in complex rearrangements, has been identified in about 5% of the cases; it should be noted that a cytogenetically, but not molecularly, indistinguishable 12;22-translocation has been identified as the characteristic aberration inclear cell sarcoma of the tendons and aponeuroses
  • among the few cases reported as pure round cell liposarcoma that have been investigated cytogenetically, t(12;16) is rare and the majority of cases have had fairly complex, unspecific aberrations
  • Cytogenetics Molecular the molecular genetic consequences of the t(12;16) is the formation of a fusion gene, involving FUS in 16p11 and CHOP in 12q13, encoding a chimeric protein; different fusion transcripts have been identified, containing the 5 promotor part of FUS, most often with exons 1-5 or alternatively either exons 1-7 or 1-8, and the entire coding region of CHOP, i.e., exons 1-4 or 2-4; this gene fusion may be identified by RT-PCR as well as by genomic PCR; the CHOP protein belongs to the C/EBP family of basic leucin zipper group of transcription factors
  • the rearrangements involving 12q13 and 22q12 result in a related gene fusion, affecting the EWS and CHOP genes; thus, the two closely related genes FUS and EWS seem to be interchangable when fused to CHOP; both FUS and EWS carry a central RNA-binding RNP-1 motif, and possibly these proteins can also bind to DNA

  • Cytogenetics
    Pleomorphic liposarcoma
    few cases have been cytogenetically characterized; they invariably show complex karyotypic changes, with no characteristic changes identified, and an extensive intratumor heterogeneity

    Other genes implicated (Data extracted from papers in the Atlas)


    Translocations implicated (Data extracted from papers in the Atlas)

     t(12;16)(q13;p11) FUS/DDIT3
     t(12;22)(q13;q12) EWSR1/DDIT3

    External links

    Mitelman databaseTopo ( Soft_tissue ) - Mitelman database (CGAP - NCBI)
    t(12;16)(q13;p11) - Mitelman database (CGAP - NCBI)
    t(12;22)(q13;q12) - Mitelman database (CGAP - NCBI)
    COSMICHisto = - Site = soft_tissue (COSMIC)
    arrayMapTopo ( C47,C49) arrayMap (Zurich)


    Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11).
    Aman P, Ron D, Mandahl N, Fioretos T, Heim S, Arheden K, Willn H, Rydholm A, Mitelman F
    Genes, chromosomes & cancer. 1992 ; 5 (4) : 278-285.
    PMID 1283316
    Cytogenetic findings in liposarcoma correlate with histopathologic subtypes.
    Sreekantaiah C, Karakousis CP, Leong SP, Sandberg AA
    Cancer. 1992 ; 69 (10) : 2484-2495.
    PMID 1568170
    Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma.
    Crozat A, Aman P, Mandahl N, Ron D
    Nature. 1993 ; 363 (6430) : 640-644.
    PMID 8510758
    Cytogenetic and fluorescence in situ hybridization investigation of ring chromosomes characterizing a specific pathologic subgroup of adipose tissue tumors.
    Dal Cin P, Kools P, Sciot R, De Wever I, Van Damme B, Van de Ven W, Van den Berghe H
    Cancer genetics and cytogenetics. 1993 ; 68 (2) : 85-90.
    PMID 8353809
    p53 Mutation and MDM2 amplification in human soft tissue sarcomas.
    Leach FS, Tokino T, Meltzer P, Burrell M, Oliner JD, Smith S, Hill DE, Sidransky D, Kinzler KW, Vogelstein B
    Cancer research. 1993 ; 53 (10 Suppl) : 2231-2234.
    PMID 8387391
    Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma.
    Rabbitts TH, Forster A, Larson R, Nathan P
    Nature genetics. 1993 ; 4 (2) : 175-180.
    PMID 7503811
    CHOP (GADD153) and its oncogenic variant, TLS-CHOP, have opposing effects on the induction of G1/S arrest.
    Barone MV, Crozat A, Tabaee A, Philipson L, Ron D
    Genes & development. 1994 ; 8 (4) : 453-464.
    PMID 8125258
    Cytogenetic aberrations in 188 benign and borderline adipose tissue tumors.
    Mandahl N, Hglund M, Mertens F, Rydholm A, Willn H, Brosj O, Mitelman F
    Genes, chromosomes & cancer. 1994 ; 9 (3) : 207-215.
    PMID 7515663
    Nonrandom secondary chromosome aberrations in liposarcomas with t(12;16).
    Mandahl N, Mertens F, Ǭman P, Rydholm A, BrosjǬ O, Willɬn H, Mitelman F
    Int J Oncol. 1994 ; 4 : 307-310.
    Characterization of the CHOP breakpoints and fusion transcripts in myxoid liposarcomas with the 12;16 translocation.
    Panagopoulos I, Mandahl N, Ron D, Hglund M, Nilbert M, Mertens F, Mitelman F, Aman P
    Cancer research. 1994 ; 54 (24) : 6500-6503.
    PMID 7987849
    Complex composition and co-amplification of SAS and MDM2 in ring and giant rod marker chromosomes in well-differentiated liposarcoma.
    Pedeutour F, Suijkerbuijk RF, Forus A, Van Gaal J, Van de Klundert W, Coindre JM, Nicolo G, Collin F, Van Haelst U, Huffermann K
    Genes, chromosomes & cancer. 1994 ; 10 (2) : 85-94.
    PMID 7520271
    Molecular abnormalities of MDM-2 in human sarcomas.
    BuesoRamos CE, Yang Y, Manshouri T, Feltz L, Ayala A, Glassman AB, Albitar M
    Int J Oncol. 1995 ; 7 : 1043-1048.
    Inflammatory Bowel Disease Questionnaire: cross-cultural adaptation and further validation.
    de Boer AG, Wijker W, Bartelsman JF, de Haes HC
    European journal of gastroenterology & hepatology. 1995 ; 7 (11) : 1043-1050.
    PMID 8680903
    Comparative genomic hybridization analysis of human sarcomas: I. Occurrence of genomic imbalances and identification of a novel major amplicon at 1q21-q22 in soft tissue sarcomas.
    Forus A, Weghuis DO, Smeets D, Fodstad O, Myklebost O, van Kessel AG
    Genes, chromosomes & cancer. 1995 ; 14 (1) : 8-14.
    PMID 8527390
    Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis.
    Knight JC, Renwick PJ, Cin PD, Van den Berghe H, Fletcher CD
    Cancer research. 1995 ; 55 (1) : 24-27.
    PMID 7805034
    MDM2 gene amplification in bone and soft-tissue tumors: Association with tumor progression in differentiated adipose-tissue tumors.
    Nakayama T, Toguchida J, Wadayama B, Kanoe H, Kotoura Y, Sasaki MS
    Int J Cancer (Pred Oncol). 1995 ; 64 : 342-346.
    Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS.
    Aman P, Panagopoulos I, Lassen C, Fioretos T, Mencinger M, Toresson H, Hglund M, Forster A, Rabbitts TH, Ron D, Mandahl N, Mitelman F
    Genomics. 1996 ; 37 (1) : 1-8.
    PMID 8921363
    Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the Chromosomes and Morphology (CHAMP) Collaborative Study Group.
    Fletcher CD, Akerman M, Dal Cin P, de Wever I, Mandahl N, Mertens F, Mitelman F, Rosai J, Rydholm A, Sciot R, Tallini G, van den Berghe H, van de Ven W, Vanni R, Willen H
    The American journal of pathology. 1996 ; 148 (2) : 623-630.
    PMID 8579124
    Genomic PCR detects tumor cells in peripheral blood from patients with myxoid liposarcoma.
    Panagopoulos I, Aman P, Mertens F, Mandahl N, Rydholm A, Bauer HF, Mitelman F
    Genes, chromosomes & cancer. 1996 ; 17 (2) : 102-107.
    PMID 8913727
    Fusion of the EWS and CHOP genes in myxoid liposarcoma.
    Panagopoulos I, Hglund M, Mertens F, Mandahl N, Mitelman F, Aman P
    Oncogene. 1996 ; 12 (3) : 489-494.
    PMID 8637704
    Combined morphologic and karyotypic study of 59 atypical lipomatous tumors. Evaluation of their relationship and differential diagnosis with other adipose tissue tumors (a report of the CHAMP Study Group).
    Rosai J, Akerman M, Dal Cin P, DeWever I, Fletcher CD, Mandahl N, Mertens F, Mitelman F, Rydholm A, Sciot R, Tallini G, Van den Berghe H, Van de Ven W, Vanni R, Willen H
    The American journal of surgical pathology. 1996 ; 20 (10) : 1182-1189.
    PMID 8827023
    Gains and losses of DNA sequences in liposarcomas evaluated by comparative genomic hybridization.
    Szymanska J, Tarkkanen M, Wiklund T, Virolainen M, Blomqvist C, Asko-Seljavaara S, Tukiainen E, Elomaa I, Knuutila S
    Genes, chromosomes & cancer. 1996 ; 15 (2) : 89-94.
    PMID 8834171
    Combined morphologic and karyotypic study of 28 myxoid liposarcomas. Implications for a revised morphologic typing, (a report from the CHAMP Group).
    Tallini G, Akerman M, Dal Cin P, De Wever I, Fletcher CD, Mandahl N, Mertens F, Mitelman F, Rosai J, Rydholm A, Sciot R, Van den Berghe H, Van den Ven W, Vanni R, Willen H
    The American journal of surgical pathology. 1996 ; 20 (9) : 1047-1055.
    PMID 8764741
    Interphase cytogenetic analysis of myxoid soft tissue tumors by fluorescence in situ hybridization and DNA flow cytometry using paraffin-embedded tissue.
    Aoki T, Hisaoka M, Kouho H, Hashimoto H, Nakata H
    Cancer. 1997 ; 79 (2) : 284-293.
    PMID 9010102
    HMGIC, the gene for an architectural transcription factor, is amplified and rearranged in a subset of human sarcomas.
    Berner JM, Meza-Zepeda LA, Kools PF, Forus A, Schoenmakers EF, Van de Ven WJ, Fodstad O, Myklebost O
    Oncogene. 1997 ; 14 (24) : 2935-2941.
    PMID 9205100
    Distinct mdm2/p53 expression patterns in liposarcoma subgroups: implications for different pathogenetic mechanisms.
    Pilotti S, Della Torre G, Lavarino C, Di Palma S, Sozzi G, Minoletti F, Rao S, Pasquini G, Azzarelli A, Rilke F, Pierotti MA
    The Journal of pathology. 1997 ; 181 (1) : 14-24.
    PMID 9071998
    Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia.
    Panagopoulos I, Lassen C, Isaksson M, Mitelman F, Mandahl N, Aman P
    Oncogene. 1997 ; 15 (11) : 1357-1362.
    PMID 9315104
    Complexity of 12q13-22 amplicon in liposarcoma: microsatellite repeat analysis.
    Wolf M, Aaltonen LA, Szymanska J, Tarkkanen M, Blomqvist C, Berner JM, Myklebost O, Knuutila S
    Genes, chromosomes & cancer. 1997 ; 18 (1) : 66-70.
    PMID 8993982
    Chromosomal organization of amplified chromosome 12 sequences in mesenchymal tumors detected by fluorescence in situ hybridization.
    Gisselsson D, Hglund M, Mertens F, Mitelman F, Mandahl N
    Genes, chromosomes & cancer. 1998 ; 23 (3) : 203-212.
    PMID 9790500
    Nonrandom pattern of telomeric associations in atypical lipomatous tumors with ring and giant marker chromosomes.
    Mandahl N, Mertens F, Willn H, Rydholm A, Kreicbergs A, Mitelman F
    Cancer genetics and cytogenetics. 1998 ; 103 (1) : 25-34.
    PMID 9595041
    Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with morphologic and clinical features: a report of the CHAMP Study Group. Chromosomes and MorPhology.
    Mertens F, Fletcher CD, Dal Cin P, De Wever I, Mandahl N, Mitelman F, Rosai J, Rydholm A, Sciot R, Tallini G, Van den Berghe H, Vanni R, Willn H
    Genes, chromosomes & cancer. 1998 ; 22 (1) : 16-25.
    PMID 9591630
    Fusion genes in solid tumors.
    Aman P
    Seminars in cancer biology. 1999 ; 9 (4) : 303-318.
    PMID 10448117
    The structure and dynamics of ring chromosomes in human neoplastic and non-neoplastic cells.
    Gisselsson D, Hglund M, Mertens F, Johansson B, Dal Cin P, Van den Berghe H, Earnshaw WC, Mitelman F, Mandahl N
    Human genetics. 1999 ; 104 (4) : 315-325.
    PMID 10369161
    Characteristics of genomic breakpoints in TLS-CHOP translocations in liposarcomas suggest the involvement of Translin and topoisomerase II in the process of translocation.
    Kanoe H, Nakayama T, Hosaka T, Murakami H, Yamamoto H, Nakashima Y, Tsuboyama T, Nakamura T, Ron D, Sasaki MS, Toguchida J
    Oncogene. 1999 ; 18 (3) : 721-729.
    PMID 9989822
    Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors.
    Pedeutour F, Forus A, Coindre JM, Berner JM, Nicolo G, Michiels JF, Terrier P, Ranchere-Vince D, Collin F, Myklebost O, Turc-Carel C
    Genes, chromosomes & cancer. 1999 ; 24 (1) : 30-41.
    PMID 9892106
    GLI gene expression in bone and soft tissue sarcomas of adult patients correlates with tumor grade.
    Stein U, Eder C, Karsten U, Haensch W, Walther W, Schlag PM
    Cancer research. 1999 ; 59 (8) : 1890-1895.
    PMID 10213497
    Identification of genes differentially expressed in TLS-CHOP carrying myxoid liposarcomas.
    Thelin-Jrnum S, Lassen C, Panagopoulos I, Mandahl N, Aman P
    International journal of cancer. Journal international du cancer. 1999 ; 83 (1) : 30-33.
    PMID 10449603
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    Written05-2000Nils Mandahl


    This paper should be referenced as such :
    Mandahl, N
    Soft tissue tumors: Liposarcoma / malignant lipomatous tumors
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):138-141.
    Free online version   Free pdf version   [Bibliographic record ]
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    indexed on : Fri Sep 5 13:17:13 CEST 2014

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