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Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2002-01-0008.

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Submitted January 3, 2002
Accepted April 29, 2002

A molecular compendium of genes expressed in multiple myeloma

Jaime O Claudio, Esther Masih-Khan, Hongchang Tang, Jason Goncalves, Michael Voralia, Zhi Hua Li, Vincent Nadeem, Eva Cuckerman, Ofelia Francisco-Pabalan, Choong Chin Liew, James R Woodgett, and A K Stewart*

Division of Experimental Therapeutics, University Health Network, Toronto, Ontario, Canada
Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada
Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; The Cardiovascular Genome Unit, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

* Corresponding author; email: kstewart{at}uhnres.utoronto.ca.

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 9,732 non-redundant expressed genes. This dataset 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 4,300 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 non-myeloma cell lines. These do 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 catalogue 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.


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