A molecular compendium of genes expressed in multiple myeloma

Jaime O. Claudio, Esther Masih-Khan, Hongchang Tang, Jason Gonçalves, Michael Voralia, Zhi Hua Li, Vincent Nadeem, Eva Cukerman, Ofelia Francisco-Pabalan, Choong Chin Liew, James R. Woodgett, A. Keith Stewart

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

We have created a molecular resource of genes expressed in primary malignant plasma cells using a combination of cDNA library construction, 5′ end single-pass sequencing, bioinformatics, and microarray analysis. In total, we identified 9732 nonredundant expressed genes. This data-set is available as the Myeloma Gene Index (www.uhnres.utoronto.ca/akstewart_lab). Predictably, the sequenced profile of myeloma cDNAs mirrored the known function of immunoglobulin-producing, high-respiratory rate, low-cycling, terminally differentiated plasma cells. Nevertheless, approximately 10% of myeloma-expressed sequences matched only entries in the database of Expressed Sequence Tags (dbEST) or the high-throughput genomic sequence (htgs) database. Numerous novel genes of potential biologic significance were identified. We therefore spotted 4300 sequenced cDNAs on glass slides creating a myeloma-enriched microarray. Several of the most highly expressed genes identified by sequencing, such as a novel putative disulfide isomerase (MGC3178), tumor rejection antigen TRA1, heat shock 70-kDa protein 5, and annexin A2, were also differentially expressed between myeloma and B lymphoma cell lines using this myeloma-enriched microarray. Furthermore, a defined subset of 34 up-regulated and 18 down-regulated genes on the array were able to differentiate myeloma from nonmyeloma cell lines. These not only include genes involved in B-cell biology such as syndecan, BCMA, PIM2, MUM1/IRF4, and XBP1, but also novel uncharacterized genes matching sequences only in the public databases. In summary, our expressed gene catalog and myeloma-enriched microarray contains numerous genes of unknown function and may complement other commercially available arrays in defining the molecular portrait of this hematopoietic malignancy.

Original languageEnglish (US)
Pages (from-to)2175-2186
Number of pages12
JournalBlood
Volume100
Issue number6
DOIs
StatePublished - Sep 15 2002

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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