Project description:Based on the transcriptome analysis of 555 sarcomas, we identified a group of tightly clustered leiomyosarcomas (LMS) due to their gene expression homogeneity. We named them “hLMS” and the other LMS “oLMS”. We derived a transcriptional signature able to identify each group and used it to classify patients from two independent cohorts. In all cohorts, hLMS were preferentially carried by women, located in the internal trunk, highly differentiated, and similarly altered at the genomic level. Based on integrative bioinformatic analysis, we show that hLMS originate from vascular smooth muscle cells presenting both contractile and synthetic characteristics, while oLMS could derive from fibroblasts. We found strong MYOCD expression to be an hLMS-specific driver and show that the MYOCD/SRF axis is essential only for hLMS survival. Identification of hLMS could become standard clinical practice, leading to the development of specific effective treatments with MYOCD/SRF inhibitors.
Project description:Genome-wide DNA methylation profiles of well-differentiated liposarcomas (WDLPS), dedifferentiated liposarcomas (DDLPS), and normal adipose tissues
Project description:Gene expression profiling reveals a potential role of APC 50% or APC 80% in stimulating hair growth in dermal papilla cells. HFDPCs were human primary cells line, treated with 5 μg/ml APC 50% for 48 h. Microarray gene expression profiling was conducted for three biological replicates HFDPCs were human primary cells line, treated with 5 μg/ml APC 80% for 48 h. Microarray gene expression profiling was conducted for three biological replicates
Project description:Genome-wide DNA methylation profiles of well-differentiated liposarcomas (WDLPS), dedifferentiated liposarcomas (DDLPS), and normal adipose tissues II
Project description:Soft tissue sarcomas are aggressive mesenchymal cancers that affect more than 10,600 new patients per year in the US, about 40% of whom will die of their disease. Soft tissue sarcomas exhibit remarkable histologic diversity, with more than 50 recognized subtypes, but our knowledge of their genomic alterations is limited. Here we describe the results of an integrative analysis of DNA sequence, copy number, and mRNA expression in 207 samples encompassing seven major subtypes. Genes mutated in more than 5% of samples within a subtype were KIT (in gastrointestinal stromal cell tumors, or GISTs), TP53 (pleomorphic liposarcomas), PIK3CA (myxoid/round-cell liposarcoma), and NF1 (both myxofibrosarcoma and pleomorphic liposarcoma). We show evidence that PIK3CA mutations, found in 18% of myxoid/round-cell liposarcomas, activate AKT in vivo and are associated with poor outcomes. Point mutations in the tumor suppressor gene NF1 were discovered in both myxofibrosarcomas and pleomorphic liposarcomas, while genomic deletions were observed in all subtypes at varying frequencies. Finally, we found that short hairpin RNA-based knockdown of a subset of genes that are amplified in dedifferentiated liposarcoma, including CDK4 and YEATS4, decreased cell proliferation. Our study yields the most detailed map of molecular alterations across diverse sarcoma subtypes to date and provides potential subtype-specific targets for therapy.
Project description:250k Sty, 250k Nsp, 250k Hind and 250k Xba Affymetrix SNP arrays for 50 leukemia remission samples used as controls for copy number analysis for GSE9109 and GSE9112. Keywords: Acute leukemia, BCR-ABL1, chronic myeloid leukemia, copy number analysis, loss-of-heterozygosity, genomics *** Due to privacy concerns, the primary SNP array data is no longer available with unrestricted access. Individuals wishing to obtain this data for research purposes may request access using the Web links below. ***
Project description:Soft tissue sarcomas are aggressive mesenchymal cancers that affect more than 10,600 new patients per year in the US, about 40% of whom will die of their disease. Soft tissue sarcomas exhibit remarkable histologic diversity, with more than 50 recognized subtypes, but our knowledge of their genomic alterations is limited. Here we describe the results of an integrative analysis of DNA sequence, copy number, and mRNA expression in 207 samples encompassing seven major subtypes. Genes mutated in more than 5% of samples within a subtype were KIT (in gastrointestinal stromal cell tumors, or GISTs), TP53 (pleomorphic liposarcomas), PIK3CA (myxoid/round-cell liposarcoma), and NF1 (both myxofibrosarcoma and pleomorphic liposarcoma). We show evidence that PIK3CA mutations, found in 18% of myxoid/round-cell liposarcomas, activate AKT in vivo and are associated with poor outcomes. Point mutations in the tumor suppressor gene NF1 were discovered in both myxofibrosarcomas and pleomorphic liposarcomas, while genomic deletions were observed in all subtypes at varying frequencies. Finally, we found that short hairpin RNA-based knockdown of a subset of genes that are amplified in dedifferentiated liposarcoma, including CDK4 and YEATS4, decreased cell proliferation. Our study yields the most detailed map of molecular alterations across diverse sarcoma subtypes to date and provides potential subtype-specific targets for therapy.