Doxorubicin resistance in a novel in vitro model of human pleomorphic liposarcoma associated with alternative lengthening of telomeres.

[pleomorphic liposarcoma]

Soft tissue sarcomas are a diverse set of fatal human tumors where few agents have demonstrable clinical efficacy , with the standard therapeutic combination of doxorubicin and ifosfamide showing only a 25 % to 30 % response rate in large multi-institutional trials . Although liposarcomas are the most common histologic form of adult soft tissue sarcomas , research in this area is severely hampered by the lack of experimentally tractable in vitro model systems . To this end , here we describe a novel in vitro model for human pleomorphic liposarcoma . The cell line (LS 2 ) is derived from a pleomorphic liposarcoma that uses the alternative lengthening of telomeres (ALT ) mechanism of telomere maintenance , which may be important in modulating the response of this tumor type to DNA-damaging agents . We present detailed baseline molecular and genomic data , including genome-wide copy number and transcriptome profiles , for this model compared with its parental tumor and a panel of liposarcomas covering multiple histologies . The model has retained essentially all of the detectable alterations in copy number that are seen in the parental tumor , and shows molecular karyotypic and expression profiles consistent with pleomorphic liposarcomas . We also show the utility of this model , together with two additional human liposarcoma cell lines , to investigate the relationship between topoisomerase 2 A expression and the sensitivity of ALT -positive liposarcomas to doxorubicin . This model , together with its associated baseline data , provides a powerful new tool to develop treatments for this clinically poorly tractable tumor and to investigate the contribution that ALT makes to modulating sensitivity to doxorubicin .

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pleomorphic liposarcoma

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