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The epigenetic reader protein SPIN1 controls proliferation and survival of liposarcoma by modulating the RET signaling pathway [ChIP-Seq]

ABSTRACT: The aim of this study is to identify the SPIN1 target genes in liposarcoma cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE57499 | GEO | 2017/02/09

SECONDARY ACCESSION(S): PRJNA246554

REPOSITORIES: GEO

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The epigenetic reader protein SPIN1 controls proliferation and survival of liposarcoma by modulating the RET signaling pathway [RNA-Seq]

Project description:The aim of this study is to identify the SPIN1 target genes in liposarcoma cells

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The epigenetic reader protein SPIN1 controls proliferation and survival of liposarcoma by modulating the RET signaling pathway

Project description:This SuperSeries is composed of the SubSeries listed below.

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The histone code reader SPIN1 controls RET signaling in liposarcoma.

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Project description:We report developmental defects in Spin1(Myf5-Cre) mice, in which Spin1 is ablated in skeletal muscle.

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Gene expression signatures in SPIN1 siRNA- and negative control-transfected breast cancer cell line MCF-7/ADM

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Project description:Liposarcoma is the most common soft tissue sarcoma, accounting for about 20% of cases. Liposarcoma is classified into 5 histologic subtypes that fall into 3 biological groups characterized by specific genetic alterations. To identify genes that contribute to liposarcomagenesis and to better predict outcome for patients with the disease, we undertook expression profiling of liposarcoma. U133A expression profiling was performed on 140 primary liposarcoma samples, which were randomly split into training set (n=95) and test set (n=45). A multi-gene predictor for distant recurrence-free survival (DRFS) was developed using the supervised principal component method. Expression levels of the 588 genes in the predictor were used to calculate a risk score for each patient. In validation of the predictor in the test set, patients with low risk score had a 3-year DRFS of 83% vs. 45% for high risk score patients (P=0.001). The hazard ratio for high vs. low score, adjusted for histologic subtype, was 4.42 (95% confidence interval 1.26-15.55; P=0.021). The concordance probability for risk score was 0.732. Genes related to adipogenesis, DNA replication, mitosis, and spindle assembly checkpoint control were all highly represented in the multi-gene predictor. Three genes from the predictor, TOP2A, PTK7, and CHEK1, were found to be overexpressed in liposarcoma samples of all five subtypes and in liposarcoma cell lines. Knockdown of these genes in liposarcoma cell lines reduced proliferation and invasiveness and increased apoptosis. Thus, genes identified from this predictor appear to have roles in liposarcomagenesis and have promise as therapeutic targets. In addition, the multi-gene predictor will improve risk stratification for individual patients with liposarcoma.

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