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Sarcoma  2011 

Liposarcoma: Molecular Genetics and Therapeutics

DOI: 10.1155/2011/483154

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Sarcomas are a group of heterogeneous tumours with varying genetic basis. Cytogenetic abnormalities range from distinct genomic rearrangements such as pathognomonic translocation events and common chromosomal amplification or loss, to more complex rearrangements involving multiple chromosomes. The different subtypes of liposarcoma are spread across this spectrum and constitute an interesting tumour type for molecular review. This paper will outline molecular pathogenesis of the three main subtypes of liposarcoma: well-differentiated/dedifferentiated, myxoid/round cell, and pleomorphic liposarcoma. Both the molecular basis and future avenues for therapeutic intervention will be discussed. 1. Introduction An estimated 13,000 people were diagnosed with soft tissue and bone sarcoma in 2009 in America, of which liposarcomas constitute 20% [1, 2]. Despite their rarity these tumours have substantial morbidity and mortality, depending on histological subtype, tumour location, and volume with retroperitoneal sarcomas having particularly poor prognosis [3–9]. Liposarcomas may be classified morphologically into 3 main subtypes consisting of: well-differentiated liposarcoma/de-differentiated liposarcoma (WD/DDLPS), myxoid/round cell liposarcoma (MLPS) and pleomorphic liposarcoma (PLPS) [10]. The morphological diversity of liposarcoma reflects the great variation in biological behaviour ranging from tumours with low metastatic potential, that is, WDLPS, to tumours with high propensity to metastasise, that is, the round cell (RC) variant of MLPS or PLPS [11]. In addition to histological characteristics, anatomical location impacts upon prognosis, given that local control is a prime concern for curative intent. Treatment is multimodal with surgical removal and radiotherapy used as cornerstones for local control, along with chemotherapy for systemic disease. Few therapeutic options are available for aggressive local or metastatic disease. Chemotherapy sensitivity varies considerably between subtypes with higher response rates in MLPS compared with WD/DDLPS (48% versus 11%) [12]. MLPS tumours are also highly radiosensitive [13, 14]. Given the small subgroup that is chemo-sensitive, and the overriding lack of chemo-curative disease there are avenues and a need for novel molecular therapies. A recent histological and molecular review of 163 liposarcoma and lipomas at the Netherlands Cancer Institute resulted in 23% of tumours being reclassified based on cytogenetic information. This highlights the importance of molecular classification in these tumours and genetic


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