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Fluorescence in situ hybridization analysis of aneuploidization patterns in monoclonal gammopathy of undetermined significance versus multiple myeloma and plasma cell leukemia.
Cancer. 2003 Feb 01; 97(3):601-9.C

Abstract

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.

Authors+Show Affiliations

Servicio General de Citometría, Centro de Investigación del Cáncer, Universidad de Salamanca, Salamanca, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

12548602

Citation

Rasillo, Ana, et al. "Fluorescence in Situ Hybridization Analysis of Aneuploidization Patterns in Monoclonal Gammopathy of Undetermined Significance Versus Multiple Myeloma and Plasma Cell Leukemia." Cancer, vol. 97, no. 3, 2003, pp. 601-9.
Rasillo A, Tabernero MD, Sánchez ML, et al. Fluorescence in situ hybridization analysis of aneuploidization patterns in monoclonal gammopathy of undetermined significance versus multiple myeloma and plasma cell leukemia. Cancer. 2003;97(3):601-9.
Rasillo, A., Tabernero, M. D., Sánchez, M. L., Pérez de Andrés, M., Martín Ayuso, M., Hernández, J., Moro, M. J., Fernández-Calvo, J., Sayagués, J. M., Bortoluci, A., San Miguel, J. F., & Orfao, A. (2003). Fluorescence in situ hybridization analysis of aneuploidization patterns in monoclonal gammopathy of undetermined significance versus multiple myeloma and plasma cell leukemia. Cancer, 97(3), 601-9.
Rasillo A, et al. Fluorescence in Situ Hybridization Analysis of Aneuploidization Patterns in Monoclonal Gammopathy of Undetermined Significance Versus Multiple Myeloma and Plasma Cell Leukemia. Cancer. 2003 Feb 1;97(3):601-9. PubMed PMID: 12548602.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fluorescence in situ hybridization analysis of aneuploidization patterns in monoclonal gammopathy of undetermined significance versus multiple myeloma and plasma cell leukemia. AU - Rasillo,Ana, AU - Tabernero,María Dolores, AU - Sánchez,María Luz, AU - Pérez de Andrés,Martín, AU - Martín Ayuso,Marta, AU - Hernández,José, AU - Moro,María Jesús, AU - Fernández-Calvo,Javier, AU - Sayagués,José María, AU - Bortoluci,Aglae, AU - San Miguel,Jesús Fernando, AU - Orfao,Alberto, PY - 2003/1/28/pubmed PY - 2003/2/13/medline PY - 2003/1/28/entrez SP - 601 EP - 9 JF - Cancer JO - Cancer VL - 97 IS - 3 N2 - 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. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/12548602/Fluorescence_in_situ_hybridization_analysis_of_aneuploidization_patterns_in_monoclonal_gammopathy_of_undetermined_significance_versus_multiple_myeloma_and_plasma_cell_leukemia_ L2 - https://doi.org/10.1002/cncr.11100 DB - PRIME DP - Unbound Medicine ER -