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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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Blood, 15 September 2002, Vol. 100, No. 6, pp. 2175-2186
NEOPLASIA
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, and
A. Keith Stewart
From the Division of Experimental Therapeutics, Toronto
General Research Institute, and from Ontario Cancer Institute,
University Health Network; both of Toronto, ON; and the Cardiovascular
Genome Unit, Brigham and Women's Hospital, Harvard Medical School,
Boston, MA.
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 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 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.
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