Transcriptomics

Dataset Information

18

Transcription profiling of human multiple myeloma patients classified using the TC system to provide a molecular characterization of the TC groups


ABSTRACT: PURPOSE. The deregulation of CCND1, CCND2 and CCND3 genes represents a common event in multiple myeloma (MM). The recently proposed TC classification grouped MM patients into five classes on the basis of their cyclins D expression profiles and the presence of the main translocations involving the immunoglobulin heavy-chain locus (IGH) at 14q32. In this study, we provide a molecular characterization of the identified TC groups. MATERIALS AND METHODS. The gene expression profiles of purified plasma cells from 50 MM cases were used to stratify the samples into the five TC classes and identify their transcriptional fingerprints. The cyclin D expression data were validated by means of real-time quantitative PCR analysis; fluorescence in-situ hybridization was used to investigate the cyclin D loci arrangements, and to detect the main IGH translocations and the chromosome 13q deletion. RESULTS. Class-prediction analysis identified 112 probe sets as characterizing the TC1, TC2, TC4 and TC5 groups, whereas the TC3 samples showed heterogeneous phenotypes and no marker genes. The TC2 group, which showed extra copies of the CCND1 locus and no IGH translocations or the chromosome 13q deletion, was characterized by the overexpression of genes involved in protein biosynthesis at translational level. A meta-analysis of published datasets validated the identified gene expression signatures. CONCLUSIONS. Our data contribute to the understanding of the molecular and biological features of distinct MM subtypes. The identification of a distinctive gene expression pattern in TC2 patients may improve risk stratification and indicate novel therapeutic targets. Experiment Overall Design: This series of microarray experiments contains the gene expression profiles of purified plasma cells (PCs) obtained from 50 newly diagnosed multiple myeloma (MM). PCs were purified from bone marrow specimens, after red blood cell lysis with 0.86% ammonium chloride, using CD138 immunomagnetic microbeads. The purity of the positively selected PCs was assessed by morphology and flow cytometry and was > 90% in all cases. 5 micrograms of total RNA was processed and hybridized to the Affymetrix HG-U133A chip following the manufacturer's instructions.

ORGANISM(S): Homo sapiens  

DISEASE(S): Multiple Myeloma Tc2,Multiple Myeloma Tc1,Multiple Myeloma Tc5,Multiple Myeloma Tc4,Multiple Myeloma Tc3

SUBMITTER: Antonino Neri  

PROVIDER: E-GEOD-2912 | ArrayExpress | 2007-10-27

SECONDARY ACCESSION(S): GSE2912GDS1284PRJNA92601

REPOSITORIES: GEO, ArrayExpress

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Publications

Molecular classification of multiple myeloma: a distinct transcriptional profile characterizes patients expressing CCND1 and negative for 14q32 translocations.

Agnelli Luca L   Bicciato Silvio S   Mattioli Michela M   Fabris Sonia S   Intini Daniela D   Verdelli Donata D   Baldini Luca L   Morabito Fortunato F   Callea Vincenzo V   Lombardi Luigia L   Neri Antonino A  

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20050829 29


PURPOSE: The deregulation of CCND1, CCND2 and CCND3 genes represents a common event in multiple myeloma (MM). A recently proposed classification grouped MM patients into five classes on the basis of their cyclin D expression profiles and the presence of the main translocations involving the immunoglobulin heavy chain locus (IGH) at 14q32. In this study, we provide a molecular characterization of the identified translocations/cyclins (TC) groups. MATERIALS AND METHODS: The gene expression profile  ...[more]

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