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Blood, 1 March 2002, Vol. 99, No. 5, pp. 1745-1757
NEOPLASIA
Global gene expression profiling of multiple myeloma, monoclonal
gammopathy of undetermined significance, and normal bone marrow plasma
cells
Fenghuang Zhan,
Johanna Hardin,
Bob Kordsmeier,
Klaus Bumm,
Mingzhong Zheng,
Erming Tian,
Ralph Sanderson,
Yang Yang,
Carla Wilson,
Maurizio Zangari,
Elias Anaissie,
Christopher Morris,
Firas Muwalla,
Frits van Rhee,
Athanasios Fassas,
John Crowley,
Guido Tricot,
Bart Barlogie, and
John Shaughnessy Jr
From the Donna D. and Donald M. Lambert Laboratory of
Myeloma Genetics, Myeloma Institute for Research and Therapy, or
Department of Pathology, University of Arkansas for Medical Sciences,
Little Rock, and the Southwest Oncology Group, Fred Hutchinson Cancer
Research Center, Seattle, WA.
Bone marrow plasma cells (PCs) from 74 patients with newly
diagnosed multiple myeloma (MM), 5 with monoclonal gammopathy of undetermined significance (MGUS), and 31 healthy volunteers (normal PCs) were purified by CD138+ selection. Gene expression of
purified PCs and 7 MM cell lines were profiled using high-density
oligonucleotide microarrays interrogating about 6800 genes. On
hierarchical clustering analysis, normal and MM PCs were differentiated
and 4 distinct subgroups of MM (MM1, MM2, MM3, and MM4) were
identified. The expression pattern of MM1 was similar to normal PCs and
MGUS, whereas MM4 was similar to MM cell lines. Clinical parameters
linked to poor prognosis, abnormal karyotype (P = .002)
and high serum 2-microglobulin levels
(P = .0005), were most prevalent in MM4. Also, genes
involved in DNA metabolism and cell cycle control were overexpressed in a comparison of MM1 and MM4. In addition, using 2 and
Wilcoxon rank sum tests, 120 novel candidate disease genes were
identified that discriminate normal and malignant PCs
(P < .0001); many are involved in adhesion, apoptosis,
cell cycle, drug resistance, growth arrest, oncogenesis, signaling, and
transcription. A total of 156 genes, including FGFR3 and
CCND1, exhibited highly elevated ("spiked") expression
in at least 4 of the 74 MM cases (range, 4-25 spikes). Elevated
expression of these 2 genes was caused by the translocation
t(4;14)(p16;q32) or t(11;14)(q13;q32). Thus, novel candidate MM disease
genes have been identified using gene expression profiling and this
profiling has led to the development of a gene-based classification
system for MM.

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