title: Molecular cytogenetic aberrations in patients with multiple myeloma studied by interphase fluorescence in situ hybridization.
abstract: BACKGROUND
  Multiple myeloma (MM) is an incurable hematological disorder characterized by the accumulation of malignant plasma cells within the bone marrow (BM). The clinical heterogeneity of MM is dictated by the cytogenetic aberrations present in the clonal plasma cells (PCs). Cytogenetic studies in MM are hampered by the hypoproliferative nature of plasma cells in MM. Therefore, fluorescence in situ hybridization (FISH) analysis combined with magnetic-activated cell sorting (MACS) is an attractive alternative for evaluation of numerical and structural chromosomal changes in MM.
  
  
  METHODS
  Interphase FISH studies with three different specific probes for the regions containing 13q14.3(D13S319), 14q32(IGHC/IGHV) and 1q12(CEP1) were performed in 48 MM patients. Interphase FISH studies with LSI IGH/CCND1, LSI IGH/FGFR3, and LSI IGH/MAF probes were used to detect t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23) in patients with 14q32 rearrangement.
  
  
  RESULTS
  Molecular cytogenetic aberrations were found in 40 (83.3%) of the 48 MM patients. 13 patients (27.1%) simultaneously had 13q deletion/monosomy 13[del(13q14)], illegitimate IGH rearrangement and chromosome 1 abnormality. Del (13q14) was detected in 21 cases (43.7%), and illegitimate IGH rearrangements in 29 (60.4%) including 6 with t (11;14) and 5 with t(4;14). None of 9 patients with illegitimate IGH rearrangements and without t(11;14) or t(4;14) we detected had t(14;16)(q32;q23). 24 of the 48 MM patients (50%) had chromosome 1 abnormalities. Among 21 patients with del (13q14), 15 patients had Amp1q12;16 had IgH rearrangements. Whereas, among 27 cases without del (13q14), 8 had Amp1q12; 13 had IgH rearrangements. There was a strong association between del(13q14) and Amp1q12 ( = 8.26, p < 0.01), and between del (13q14) and IgH rearrangement ( = 3.88, p < 0.05).
  
  
  CONCLUSIONS
  13q deletion/monosomy 13, IGH rearrangement and chromosome 1 abnormality are frequent in MM. They are not randomly distributed, but strongly interconnected. Interphase FISH technique combined with MACS using CD138-specific antibody is a highly sensitive technique at detecting molecular cytogenetic aberrations in MM.
authors: Department of Hematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital Nanjing 210029, China.
authors: L- J
authors: L
authors: Chen
authors: J- Y
authors: J
authors: Li
authors: W
authors: W
authors: Xu
authors: H- R
authors: H
authors: Qiu
authors: Y
authors: Y
authors: Zhu
authors: Y- P
authors: Y
authors: Zhang
authors: L- M
authors: L
authors: Duan
authors: S- X
authors: S
authors: Qian
authors: H
authors: H
authors: Lu
mesh_terms: D000368:Aged; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D002882:Chromosomes, Human, Pair 13; D002883:Chromosomes, Human, Pair 14; D020732:Cytogenetic Analysis; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007399:Interphase; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology*; D009367:Neoplasm Staging; D053668:Syndecan-1 / Q000378:metabolism
chemical_list: D053668:Syndecan-1