Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide analysis of primary and secondary angiosarcomas using RNA extracted from formalin-fixed parafinembedded samples.

ABSTRACT: Angiosarcomas are highly malignant tumors that develop as primary angiosarcomas of unknown cause or as secondary angiosarcomas, most often following radiation therapy for breast cancer. These subsets are morphologically indistinguishable, which motivates our aim to identify genetic classifiers for diagnostic and therapeutic application. We applied the 18k whole-genome c-DNA-mediated annealing, selection, extension, and ligation (WG-DASL) assay for expression profiling of 26 primary and 29 secondary angiosarcomas. Primary and secondary angiosarcomas differed by 103 significantly de-regulated genes with up-regulation of RET, KIT, FLT4, MYC and RASGRP3 and down-regulation of CDKN2C in secondary angiosarcoma. Functional annotation analysis demonstrated involvement of multiple target genes in the receptor protein tyrosine kinase pathway. Up-regulation of RET and down-regulation of CDKN2C characterize secondary angiosarcoma, which implies a mechanistic basis for the evaluation of RET-kinase inhibitors in the treatment of these highly aggressive tumors. Total RNA obtained from primary and secondary angiosarcoma samples from formalin-fixed parafin-embedded samples were compared using WG-DASL. Biological replicates (two samples from the same patient, different parts of the tumor or different operation specimens) Technical replicates (two samples from the same patient and same tumor sample, analyzed in different areas of the bead chip)

ORGANISM(S): Homo sapiens

SUBMITTER: Emelie Styring

PROVIDER: E-GEOD-52664 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Key roles for MYC, KIT and RET signaling in secondary angiosarcomas.

Styring E E Seinen J J Dominguez-Valentin M M Domanski H A HA Jönsson M M von Steyern F V FV Hoekstra H J HJ Suurmeijer A J H AJ Nilbert M M

British journal of cancer 20140701 2

<h4>Background</h4>Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas.<h4>Methods</h4>Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 ...[more]

PMID: 24983371

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Project description:Microarray-based gene expression analysis of peripheral whole blood is a common strategy in the development of clinically relevant biomarker panels for a variety of human diseases. However, the results of such an analysis are often plagued by decreased sensitivity and reliability due to the effects of relatively high levels of globin mRNA in whole blood. Globin reduction assays have been shown to overcome such effects, but they require large amounts of total RNA and may induce distinct gene expression profiles. The Illumina whole-genome DASL (WG-DASL) assay can detect gene expression levels using partially degraded RNA samples and has the potential to detect rare transcripts present in highly heterogeneous whole blood samples without the need for globin reduction. We therefore assessed the utility of the WG-DASL assay in the analysis of peripheral whole blood gene expression profiles. We find that gene expression detection is significantly increased with the use of WG-DASL compared to the standard in vitro transcription-based direct hybridization (IVT), while globin-probe-negative WG-DASL did not exhibit significant improvements over globin-probe-positive WG-DASL. Globin reduction increases the detection sensitivity and reliability of both WG-DASL and IVT with little effect on raw intensity correlations: raw intensity correlations between total RNA and globin-reduced RNA were 0.970 for IVT and 0.981 for WG-DASL. Overall, the detection sensitivity of the WG-DASL assay is higher than the IVT-based direct hybridization assay, with or without globin reduction, and should be considered in conjunction with globin reduction methods for future blood-based gene expression studies. Peripheral whole blood samples were collected from eight human donors in PAXGene tubes. RNA was isolated after freezing and storage, and then prepared for gene expression analysis using the Illumina Human-Ref8 v3.0 BeadChip. Alpha and beta globin were reduced from a portion of the total RNA using the GLOBINclear assay (Ambion, Austin, TX, USA). Two methods of microarray target preparation were examined: Illumina IVT-based direct hybridization (IVT) and Illumina Whole-Genome DASL (WG-DASL). Two DASL Assay Oligo pools (DAP) were utilized for DASL target preparation: the DASL Assay Oligo Pool with globin probes (DAP +) and the DASL Asssay Oligo Pool without globin probes (DAP-).

Dataset Information

Genome-wide analysis of primary and secondary angiosarcomas using RNA extracted from formalin-fixed parafinembedded samples.

Publications

Key roles for MYC, KIT and RET signaling in secondary angiosarcomas.

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