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