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Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: liposarcoma

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Introduction

Liposarcoma (LPS) is the most common soft tissue sarcoma and accounts for approximately 20% of all mesenchymal malignancies [1]. Diagnostic histologic criteria for LPS have evolved over the years [2], [3], [4] and at present, LPS are divided into 3 major categories: well-differentiated, myxoid and round-cell, and pleomorphic [3]. Thus, the cytogenetic and molecular aspects of LPS will be described in this Update according to these subtypes. As in previous Updates, findings and data published since 1994 [5] will be mainly presented.

Section snippets

Some salient pathologic and clinical features of LPS

Details regarding the histopathology and clinical aspects of various types of LPS can be found in a number of authoritative texts and publications [3], [4], [5], [6], [7], [8], [9], [10], [11]. In the present Update, only those tumors will be discussed for which cytogenetic and/or molecular genetic findings have been published.

Chromosome changes in LPS

The chromosome changes in LPS will be discussed according to histologic type (Table 1).

CGH studies in LPS

Though CGH cannot establish balanced chromosomal changes, such as translocations or inversions or subtle karyotypic aberrations, and reflects an average of the genetic changes within a tumor, CGH does supply apposite information on chromosomal losses and gains to complement the cytogenetic anomalies in such tumors [114], [115], [116].

Amplification of parts of 12q13∼q22 region has been repeatedly established with CGH in a number of studies of WDLPS and dedifferentiated LPS [102], [103], [109],

Molecular studies in myxoid LPS with the TLS-CHOP fusion gene

As indicated earlier, the t(12;16)(q13;p11) characteristic of myxoid LPS [5] results in the fusion of the CHOP (also named GADD153 and DDIT3) gene located at 12q13 [128] and the TLS (FUS) gene located at 16p11 [77]. The specificity of the chimeric TLS-CHOP fusion protein in the causation of LPS has been demonstrated by its ability to induce LPS in transgenic mice [129], [130].

The CHOP gene, a member of the leucine zipper transcription factor family, is implicated in adipocyte differentiation,

Other molecular genetic changes in LPS

Ambiguity or lack of information regarding the histological types of LPS investigated in a significant number of the reports referred to in this section of the Update, should serve as a caveat concerning deductions from results presented. The roles played by much of the molecular genetic changes in LPS to be mentioned in this section remain unclear. Thus, it is not known clearly whether they are primary or secondary events. Most of the genes to be discussed appear to produce effects in

Molecular studies in dedifferentiated LPS

The low metastatic rate exhibited by 14 dedifferentiated LPS [110], when compared with other histologically high-grade pleomorphic sarcomas, might be partially explained by the integrity of the TP53 gene [110], though multivariate analysis of large, histologically homogeneous series is needed [265]. Similar immunohistochemical studies in dedifferentiated LPS showed mdm2 overexpression, which may not necessarily be related to gene amplification [182], to be a common finding in these tumors,

Comments

Skapek and Chui [266] drew attention to a number of areas of LPS concerned with strategies for therapy of these tumors. One of these areas is the involvement of a large number of genes triggered by the TLS-CHOP fusion gene in myxoid LPS [267], though the role of these induced genes in LPS development is still uncertain. Skapek and Chui [266] also indicated that research on TLS-CHOP and other fusion proteins may lead to novel therapeutic approaches addressing disruption of downstream effectors

Acknowledgments

The author wishes to thank Mrs. Molly Harrington and Mrs. Irma Contreras of the St. Joseph's Hospital and Medical Center for assistance in literature search. Jan Vaughan, as usual, deserves my thanks for the preparation of the manuscript. All figures reproduced with appropriate permission.

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References (293)

  • C. Turc-Carel et al.

    Cytogenetic studies of adipose tissue tumors. II. Recurrent reciprocal translocation t(12;16)(q13;p11) in myxoid liposarcomas

    Cancer Genet Cytogenet

    (1986)
  • S. Smith et al.

    Translocation t(12;16) in a case of myxoid liposarcoma

    Cancer Genet Cytogenet

    (1987)
  • E.F.P.M. Schoenmakers et al.

    Physical mapping of chromosome 12q breakpoints in lipoma, pleomorphic salivary gland adenoma, uterine leiomyoma, and myxoid liposarcoma

    Genomics

    (1994)
  • G. Sozzi et al.

    Relevance of cytogenetic and fluorescent in situ hybridization analyses in the clinical assessment of soft tissue sarcoma

    Hum Pathol

    (1997)
  • P. Dal Cin et al.

    Cytogenetic and fluorescence in situ hybridization investigation of ring chromosomes characterizing a specific pathologic subgroup of adipose tissue tumors

    Cancer Genet Cytogenet

    (1993)
  • F. Pedeutour et al.

    Chromosome 12 origin in rings and giant markers in well-differentiated liposarcoma

    Cancer Genet Cytogenet

    (1993)
  • N. Mandahl et al.

    Nonrandom pattern of telomeric associations in atypical lipomatous tumors with ring and giant marker chromosomes

    Cancer Genet Cytogenet

    (1998)
  • C.D. Fletcher

    Soft tissue tumours

  • S.W. Weiss et al.

    Enzinger and Weiss's soft tissue tumors

    (2001)
  • A.P. Dei Tos et al.

    Atypical lipomatous tumour/well differentiated liposarcoma

  • A.A. Sandberg et al.

    The cytogenetics of bone and soft tissue tumors

    (1994)
  • T. Mentzel et al.

    Lipomatous tumours of soft tissues: an update

    Virchows Arch

    (1995)
  • C.D. Fletcher

    Will we ever reliably predict prognosis in a patient with myxoid and round cell liposarcoma?

    Adv Anat Pathol

    (1997)
  • M. Campanacci

    Bone and soft tissue tumors

    (1999)
  • D.C. Linehan et al.

    Influence of biologic factors and anatomic site in completely resected liposarcomas

    J Clin Oncol

    (2000)
  • C.R. Antonescu et al.

    Myxoid retroperitoneal liposarcoma. Morphologic and molecular delineation from classic myxoid liposarcoma

    Mod Pathol

    (2000)
  • H.R. Chang et al.

    Multifactorial analysis of survival in primary extremity liposarcoma

    Word J Surg

    (1990)
  • P. Gustafson et al.

    Liposarcoma: A population-based epidemiologic and prognostic study of features of 43 patients, including tumor DNA content

    Int J Cancer

    (1993)
  • S.E. Kilpatrick et al.

    The clinicopathologic spectrum of myxoid and round cell liposarcoma. A study of 95 cases

    Cancer

    (1996)
  • C. Antonescu et al.

    Myxoid liposarcoma

  • A.P. Dei Tos et al.

    S-100 protein staining in liposarcoma. Its diagnostic utility in the high grade myxoid (round cell) variant

    Appl Immunohistochem

    (1996)
  • B.M. Wehrli et al.

    Myxoid liposarcoma. A Proposal for a two tier grading system

    Mod Pathol

    (2000)
  • S.E. Kilpatrick et al.

    The clinicopathologic spectrum of myxoid and round cell sarcoma: a study of 95 cases

    Cancer

    (1996)
  • E. Orvieto et al.

    Myxoid and round cell liposarcoma: A spectrum of myxoid adipocytic neoplasia

    Semin Diagn Pathol

    (2001)
  • J.C. Knight et al.

    Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: Molecular and cytogenetic analysis

    Cancer Res

    (1995)
  • M. Kuroda et al.

    Chimeric TLS/FUS-CHOP gene expression and heterogeneity of its junction in human myxoid and round cell liposarcoma

    Am J Pathol

    (1995)
  • G. Tallini et al.

    Combined morphologic and karyotypic study of 28 myxoid liposarcomas. Implications for a revised morphologic typing. A report from the CHAMP group

    Am J Surg Pathol

    (1996)
  • M. Hisaoka et al.

    Detection of TLS/FUS-CHOP fusion transcripts in myxoid and round cell liposarcomas by nested reverse transcription-polymerase chain reaction using archival paraffinembedded tissues

    Diagn Mol Pathol

    (1998)
  • T.A. Smith et al.

    Immunohistochemical analysis of p53 protein in myxoid/round-cell liposarcoma of the extremities

    Appl Immunohistochem

    (1996)
  • T.A. Smith et al.

    Myxoid/round cell liposarcoma of the extremities. A clinicopathologic study of 29 cases with particular attention to extent of round cell liposarcoma

    Am J Surg Pathol

    (1996)
  • A.P. Dei Tos et al.

    Molecular aberrations of the G1-S checkpoint in myxoid and round cell liposarcoma

    Am J Pathol

    (1997)
  • H.L. Evans

    Liposarcoma: a study of 55 cases with a reassessment of its classification

    Am J Surg Pathol

    (1979)
  • L.G. Kindblom et al.

    Atypical lipoma

    Acta Pathol Microbiol Immunol Scand [A]

    (1982)
  • S.W. Weiss et al.

    Well-differentiated liposarcoma (atypical lipoma) of deep soft tissue of the extremities, retroperitoneum, and miscellaneous sites. A follow-up study of 92 cases with analysis of the incidence of “dedifferentiation”

    Am J Surg Pathol

    (1992)
  • A.P. Dei Tos et al.

    Spindle cell liposarcoma, a hitherto unrecognized variant of liposarcoma. Analysis of six cases

    Am J Surg Pathol

    (1994)
  • A.P. Dei Tos et al.

    Coordinated expression and amplification of the MDM2, CDK4, and HMGI-C genes in atypical lipomatous tumours

    J Pathol

    (2000)
  • L. Laurino et al.

    Well-differentiated liposarcoma (atypical lipomatous tumors)

    Semin Diagn Pathol

    (2001)
  • F.M. Enzinger

    Liposarcoma. A study of 103 cases

    Virchows Arch Pathol Anat

    (1962)
  • S.W. Weiss

    Histologic typing of soft tissue tumours. World Health Organization Histological Classification of Tumours

    (1994)
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