A molecular compendium of genes expressed in multiple myeloma.
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. GenBank Accession numbers include BF169967-BF176369, BF185966-BF185969, and BF177280-BF177455.
Claudio
Jaime O
JO
Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9 Canada.
Masih-Khan
Esther
E
Tang
Hongchang
H
Gonçalves
Jason
J
Voralia
Michael
M
Li
Zhi Hua
ZH
Nadeem
Vincent
V
Cukerman
Eva
E
Francisco-Pabalan
Ofelia
O
Liew
Choong Chin
CC
Woodgett
James R
JR
Stewart
A Keith
AK
D000595:Amino Acid Sequence; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis*; D030561:Databases, Nucleic Acid; D018450:Disease Progression; D020869:Gene Expression Profiling; D015723:Gene Library; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D049294:Phospholipid Transfer Proteins; D010950:Plasma Cells; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans; D017422:Sequence Analysis, DNA; D053667:Syndecans
D017306:Annexin A2; D004273:DNA, Neoplasm; D018840:HSP70 Heat-Shock Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D011506:Proteins; D011509:Proteoglycans; D053667:Syndecans; D019704:Protein Disulfide-Isomerases