title: Identification of unbalanced genome copy number abnormalities in patients with multiple myeloma by single-nucleotide polymorphism genotyping microarray analysis.
abstract: Single-nucleotide polymorphism genotyping microarray (SNP array) analysis provides detailed information on chromosomal copy number aberrations. To obtain detailed information on genomic abnormalities related to pathogenesis or prognosis of multiple myeloma (MM), we performed 250K SNP array analysis in 39 MM patients and 11 cell lines. We identified an accumulation of deletions and uniparental disomies at 22q12.1. Among the hyperdiploid MM cases, chromosomal imbalance at this locus was associated with poor prognosis. On sequencing, we also found a mutation in the seizure-related 6 homolog (mouse)-like (SEZ6L) gene located at ch.22q12.1 in an MM cell line, NOP1. We further found isolated deletions in 17 genes, five of which are known tumor suppressor genes. Of these, deletion of protein tyrosine phosphatase, receptor type D (PTPRD) was found in three samples, including two patients. Consistent with previous reports, non-hyperdiploid MM, deletion of 13q (del13q) and gain of 1q in non-hyperdiploid MMs were predictive of poor prognosis (p = 0.039, p = 0.049, and p = 0.013, respectively). However, our analysis revealed that unless accompanied by gain of 1q, the prognosis of non-hyperdiploid MM was as good as that of hyperdiploid MM. Thus, SNP array analysis provides significant information useful to understanding the pathogenesis and prognosis of MM.
authors.affiliation: Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Kamada
authors.forename: Mamiko
authors.initials: M
authors.lastname: Sakata-Yanagimoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Sanada
authors.forename: Aiko
authors.initials: A
authors.lastname: Sato-Otsubo
authors.forename: Terukazu
authors.initials: T
authors.lastname: Enami
authors.forename: Kazumi
authors.initials: K
authors.lastname: Suzukawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Kurita
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Nishikii
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okoshi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002899:Chromosomes, Human, Pair 9; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics
chemical_list: C090899:PTPRD protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2