Dataset related to article "Mechanisms of responsiveness to and resistance against trabectedin in murine models of human myxoid liposarcoma"
Creators
- 1. Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, 20072 Pieve Emanuele - Milan, Italy AND Laboratory of Cancer Pharmacology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano - Milan, Italy
- 2. Department of Oncology, Istituto di Ricerche Farmacologiche "Mario Negri" IRCCS, via Mario Negri 2, 20156 Milan, Italy
- 3. Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK
- 4. Adult Mesenchymal Tumour Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
- 5. Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
- 6. Laboratory of Cancer Pharmacology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano - Milan, Italy
- 7. Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, 20072 Pieve Emanuele - Milan, Italy.; Laboratory of Cancer Pharmacology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano - Milan, Italy
Description
This record contains data related to article "Mechanisms of responsiveness to and resistance against trabectedin in murine models of human myxoid liposarcoma".
Myxoid liposarcoma (MLPS) is a rare soft-tissue sarcoma characterised by the expression of FUS-DDIT3 chimera. Trabectedin has shown significant clinical anti-tumour activity against MLPS. To characterise the molecular mechanism of trabectedin sensitivity and of resistance against it, we integrated genomic and transcriptomic data from treated mice bearing ML017 or ML017/ET, two patient-derived MLPS xenograft models, sensitive to and resistant against trabectedin, respectively. Longitudinal RNA-Seq analysis of ML017 showed that trabectedin acts mainly as a transcriptional regulator: 15 days after the third dose trabectedin modulates the transcription of 4883 genes involved in processes that sustain adipocyte differentiation. No such differences were observed in ML017/ET. Genomic analysis showed that prolonged treatment causes losses in 4p15.2, 4p16.3 and 17q21.3 cytobands leading to acquired-resistance against the drug. The results dissect the complex mechanism of action of trabectedin and provide the basis for novel combinatorial approaches for the treatment of MLPS that could overcome drug-resistance.
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Additional details
Related works
- Is supplement to
- 10.1016/j.ygeno.2021.07.028 (DOI)
- 3433-9817 (ISSN)