title: Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells.
abstract: 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 beta(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 chi(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.
authors.affiliation: Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, 72205, USA.
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
authors.forename: Johanna
authors.initials: J
authors.lastname: Hardin
authors.forename: Bob
authors.initials: B
authors.lastname: Kordsmeier
authors.forename: Klaus
authors.initials: K
authors.lastname: Bumm
authors.forename: Mingzhong
authors.initials: M
authors.lastname: Zheng
authors.forename: Erming
authors.initials: E
authors.lastname: Tian
authors.forename: Ralph
authors.initials: R
authors.lastname: Sanderson
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Carla
authors.initials: C
authors.lastname: Wilson
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.forename: Elias
authors.initials: E
authors.lastname: Anaissie
authors.forename: Christopher
authors.initials: C
authors.lastname: Morris
authors.forename: Firas
authors.initials: F
authors.lastname: Muwalla
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
authors.forename: Athanasios
authors.initials: A
authors.lastname: Fassas
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: John
authors.initials: J
authors.lastname: Shaughnessy
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000032:analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000145:classification* / Q000235:genetics*; D009363:Neoplasm Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010265:Paraproteinemias / Q000145:classification / Q000235:genetics*; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins