PMID- 12548602
OWN - NLM
STAT- MEDLINE
DCOM- 20030211
LR  - 20071115
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 97
IP  - 3
DP  - 2003 Feb 1
TI  - Fluorescence in situ hybridization analysis of aneuploidization patterns in 
      monoclonal gammopathy of undetermined significance versus multiple myeloma and 
      plasma cell leukemia.
PG  - 601-9
AB  - BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is a clonal 
      plasma cell (PC) disorder usually characterized by a benign clinical course. 
      However, in approximately 25% of patients, the disorder has been found to evolve 
      into a multiple myeloma (MM). The mechanism leading to the evolution of MGUS 
      remains unknown. The aim of the current study was, first, to assess by interphase 
      fluorescence in situ hybridization (FISH) the incidence of numerical 
      abnormalities of chromosomes 6, 9, 13, and 17 in MGUS patients and to compare it 
      with that found in MM and PC leukemia (PCL) patients and, second, to explore the 
      potential heterogeneity of the pathologic PC in MGUS as a way to identify unique 
      cytogenetic patterns different from those frequently observed in MM and PCL. 
      METHODS: Numerical abnormalities of chromosomes 6, 9, 13, and 17 were 
      investigated by dual- and triple-color FISH in bone marrow PC from 208 patients 
      corresponding to MGUS (n = 30), MM (n = 158), and PCL (n = 20) cases. In MGUS and 
      MM patients with < 10% PC, both normal and phenotypically aberrant PC were 
      discriminated by multiparameter flow cytometry, the latter subset being 
      specifically sorted for FISH analysis with a purity of 93% +/- 6%. RESULTS: 
      Overall, 57% of the MGUS patients displayed abnormalities for at least 1 of the 4 
      chromosomes analyzed compared with 75% of both MM and PCL cases. The most common 
      single chromosome abnormalities detected in MGUS were gains of chromosomes 9 
      (23%) and/or 6 (21%) and loss of chromosomes 13 (21%) and/or 17 (17%). Compared 
      with MM patients, MGUS patients were found to have both a lower incidence of 
      gains of chromosome 9 (23% vs. 54%, P = 0.002) and monosomy 13/13q(-) deletions 
      (21% vs. 38%, P = 0.07); with respect to PCL cases, MGUS patients were found to 
      have a lower incidence of monosomy 13/13q(-) deletions (21% vs. 75%, P < 0.001) 
      together with a slightly higher frequency of gains of both chromosomes 6 (21% vs. 
      0%, P = 0.05) and 9 (23% vs. 7%, P = 0.1). The simultaneous use of two or three 
      different chromosome probes showed that within the purified compartment of 
      phenotypically aberrant PC from most MGUS patients (67%), more than 1 PC clone 
      could be identified. In contrast, the incidence of 2 or more PC clones was much 
      lower in MM (19%, P < 0.001) and PCL (15%, P = 0.003). Interestingly, although 
      some FISH patterns were shared by both groups of diseases (i.e., monosomy 
      13/13q(-) deletions alone, gains of chromosome 9 alone or together with trisomy 
      6), others were found almost exclusively in either MGUS (i.e., a clone with 
      monosomy 6 and/or 17 together with nuclei displaying a normal chromosome number) 
      or in MM (i.e., monosomy 13/13q(-) deletions together with gains of chromosome 6 
      and/or 9). CONCLUSIONS: In summary, the results of the current study showed that 
      MGUS patients displayed a high incidence of numerical alterations, which are 
      usually associated with the presence of more than one tumor cell clone. It is 
      interesting to note that the cytogenetic patterns observed in the aneuploid PC 
      clones from MGUS patients were frequently different from those observed in both 
      MM and PCL.
CI  - Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11100
FAU - Rasillo, Ana
AU  - Rasillo A
AD  - Servicio General de Citometria, Centro de Investigacion del Cancer, Universidad 
      de Salamanca, Salamanca, Spain.
FAU - Tabernero, Maria Dolores
AU  - Tabernero MD
FAU - Sanchez, Maria Luz
AU  - Sanchez ML
FAU - Perez de Andres, Martin
AU  - Perez de Andres M
FAU - Martin Ayuso, Marta
AU  - Martin Ayuso M
FAU - Hernandez, Jose
AU  - Hernandez J
FAU - Moro, Maria Jesus
AU  - Moro MJ
FAU - Fernandez-Calvo, Javier
AU  - Fernandez-Calvo J
FAU - Sayagues, Jose Maria
AU  - Sayagues JM
FAU - Bortoluci, Aglae
AU  - Bortoluci A
FAU - San Miguel, Jesus Fernando
AU  - San Miguel JF
FAU - Orfao, Alberto
AU  - Orfao A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Aneuploidy
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human, Pair 13
MH  - Chromosomes, Human, Pair 17
MH  - Chromosomes, Human, Pair 6
MH  - Chromosomes, Human, Pair 9
MH  - Female
MH  - Humans
MH  - Immunophenotyping
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Plasma Cell/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*genetics/pathology
MH  - Paraproteinemias/*genetics/pathology
EDAT- 2003/01/28 04:00
MHDA- 2003/02/13 04:00
CRDT- 2003/01/28 04:00
PHST- 2003/01/28 04:00 [pubmed]
PHST- 2003/02/13 04:00 [medline]
PHST- 2003/01/28 04:00 [entrez]
AID - 10.1002/cncr.11100 [doi]
PST - ppublish
SO  - Cancer. 2003 Feb 1;97(3):601-9. doi: 10.1002/cncr.11100.