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Profiling DNA copy number alterations of myxofibrosarcomas with NimbleGen array CGH chips

ABSTRACT: Characterized by a wide histological spectrum, myxofibrosarcoma ranges from deceptively bland-appearing lesions to frankly pleomorphic sarcomas, representing a suitable model to elucidate the molecular aberrations in multistep disease progression. To explore cancer-associated genes of myxofibrosarcoma, ultrahigh-resolution array comparative genomic hybridization (aCGH) was used to profile DNA copy number alterations in myxofibrosarcoma tumor samples and cell lines.

ORGANISM(S): Homo sapiens

PROVIDER: GSE35483 | GEO | 2012/02/02

SECONDARY ACCESSION(S): PRJNA152373

REPOSITORIES: GEO

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Profiling DNA copy number alterations of myxofibrosarcomas with NimbleGen array CGH chips

Project description:Characterized by a wide histological spectrum, myxofibrosarcoma ranges from deceptively bland-appearing lesions to frankly pleomorphic sarcomas, representing a suitable model to elucidate the molecular aberrations in multistep disease progression. To explore cancer-associated genes of myxofibrosarcoma, ultrahigh-resolution array comparative genomic hybridization (aCGH) was used to profile DNA copy number alterations in myxofibrosarcoma tumor samples and cell lines. Along with normal reference DNA, 12 tumor samples and 2 cell lines (NMFH-1, OH931) of human myxofibrosarcoma were extracted for genomic DNAs, which were subjected to manufacturer’s (NimbleGen Inc) outsourcing service of DNA labeling, hybridization, and normalization of data obtained from 385K oligonucleotide array CGH chips.

2012-02-02 | E-GEOD-35483 | biostudies-arrayexpress

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Project description:In soft tissue sarcomas, diagnosis of malignant fibrous histiocytoma (MFH) has been a very controversial issue, and MFH is now considered to be reclassified into pleomorphic subtypes of other sarcomas. To characterize and reclassify MFH genetically, we analyzed gene expression in 105 samples from ten types of soft tissue tumors. Experiment Overall Design: Gene expression of 105 soft tissue tumor samples consisting of synovial sarcoma (n=16), myxoid liposarcoma (n=19), lipoma (n=3), well-differentiated liposarcoma (n=3), dedifferentiated liposarcoma (n=15), myxofibrosarcoma (n=15), leiomyosarcoma (n=6), malignant peripheral nerve sheath tumor (n=3), fibrosarcoma (n=4) and malignant fibrous histiocytoma (n=21) were analyzed using an Affymetrix HG-U133A array.

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Discovery-Based Protein Expression Profiling Identifies Distinct Subgroups and Pathways in Leiomyosarcomas

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Whole-transcript expression data for soft-tissue sarcoma tumors and control normal fat specimens

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. Human soft-tissue sarcoma specimens were profiled on Affymetrix U133A arrays per manufacturer's instructions.

2010-07-05 | E-GEOD-21122 | biostudies-arrayexpress

Affymetrix SNP array data for soft tissue sarcoma samples

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. Human soft tissue sarcoma samples and their matched normal DNA were profiled on Affymetrix 250K SNP (Sty) arrays per manufacturer's instructions

2010-07-05 | E-GEOD-21123 | biostudies-arrayexpress

Affymetrix SNP array data for soft tissue sarcoma samples

2010-07-06 | GSE21123 | GEO

Whole-transcript expression data for soft-tissue sarcoma tumors and control normal fat specimens

2010-07-06 | GSE21122 | GEO

Genetic Screen in a Pre-Clinical Model of Sarcoma Development Defines Drivers and Therapeutic Vulnerabilities

Project description:High-grade complex karyotype sarcomas are a heterogeneous group of more than seventy tumors that vary in histology, clinical course, and patient demographics. Despite these differences, these high-grade sarcomas are treated similarly with varying outcomes. Pre-clinical models of distinct human sarcoma subtypes would advance insights into the relationships between sarcomas and inform therapeutic decisions. We describe the transformation of human mesenchymal stem cells into multiple subtypes of high-grade sarcoma. Using a pooled genetic screening approach, we identified key drivers and potential modifiers of transformation. YAP1, KRAS, CDK4, and PIK3CA were validated as drivers of four distinct sarcoma subtypes, undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), leiomyosarcoma (LMS), and osteosarcoma (OS). Histologically and phenotypically these tumors reflect human sarcomas including the pathognomonic complex karyotype and YAP1 amplification. Transcriptome analysis confirmed that these tumors accurately recapitulate human disease. This model is a tool that can be used to begin to understand pathways and mechanisms driving human sarcoma development, the relationship between sarcoma subtypes and to identify and test new therapeutic targets for this aggressive and heterogeneous disease.

2024-08-15 | GSE228213 | GEO

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