Frequent alterations and epigenetic silencing of differentiation pathway genes in structurally rearranged liposarcomas.

ABSTRACT:

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We explored diverse alterations contributing to liposarcomagenesis by sequencing the genome, exome, transcriptome, and cytosine methylome of a primary and recurrent dedifferentiated liposarcoma (DLPS) from distinct chemotherapy/radiotherapy-naïve patients. The liposarcoma genomes had complex structural rearrangements, but in different patterns, and with varied effects on the structure and expression of affected genes. While the point mutation rate was modest, integrative analyses and additional screening identified somatic mutations in HDAC1 in 8.3% of DLPS. Liposarcoma methylomes revealed alterations in differentiation pathway genes, including CEBPA methylation in 24% of DLPS. Treatment with demethylating agents, which restored CEBPA expression in DLPS cells, was anti-p

SUBMITTER: Taylor BS 

PROVIDER: S-EPMC3274776 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature