What question did this study set out to answer?

To identify genetic and epigenetic alterations driving liposarcomagenesis and the suppression of adipocyte differentiation in dedifferentiated liposarcomas.

October 12, 2011Cancer DiscoveryOpen Access

Frequent Alterations and Epigenetic Silencing of Differentiation Pathway Genes in Structurally Rearranged Liposarcomas

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Authors

BTBarry S. TaylorPennington Biomedical Research Center PDPenelope DeCarolisSarcoma Oncology Center CAChristina V. AngelesUniversity of Michigan

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Implication

Multimodal sequencing reveals epigenetic silencing of differentiation pathways in dedifferentiated liposarcoma, indicating potential therapeutic utility for demethylating agents.

Key Points

To identify genetic and epigenetic alterations driving liposarcomagenesis and the suppression of adipocyte differentiation in dedifferentiated liposarcomas.
Performed whole-genome, exome, transcriptome, and cytosine methylome sequencing on primary and recurrent dedifferentiated liposarcomas (DLPS) from treatment-naïve patients.
Conducted validation screening for recurrent alterations across DLPS cohorts.
Evaluated the functional effects of pharmacologic DNA demethylating agents on gene re-expression, proliferation, and apoptosis in vitro and on tumor growth in vivo.
DLPS genomes exhibited complex structural rearrangements, a modest point mutation rate, and somatic mutations in HDAC1 occurring in 8.3% of DLPS cases.
Methylome profiling revealed aberrant methylation of differentiation pathway genes, including CEBPA promoter methylation in 24% of DLPS cases and selective silencing of microRNA-193b.
Demethylating agent treatment restored CEBPA expression, triggered anti-proliferative and pro-apoptotic effects in vitro, and reduced DLPS tumor growth in vivo.

Cite This Study

Taylor et al. (2011) studied this question.

synapsesocial.com/papers/6aa034a236ea76a62dc1198e https://doi.org/10.1158/2159-8290.cd-11-0181

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Implication

Multimodal sequencing reveals epigenetic silencing of differentiation pathways in dedifferentiated liposarcoma, indicating potential therapeutic utility for demethylating agents.

Frequent Alterations and Epigenetic Silencing of Differentiation Pathway Genes in Structurally Rearranged Liposarcomas

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Implication

Key Points

Cite This Study

Frequent Alterations and Epigenetic Silencing of Differentiation Pathway Genes in Structurally Rearranged Liposarcomas

Discussion

Member takes

Implication

Key Points

Cite This Study

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