Fluorescence in situ hybridization analysis of aneuploidization patterns in monoclonal gammopathy of undetermined significance versus multiple myeloma and plasma cell leukemia

• Published in: Cancer 2003-02, Vol.97 (3), p.601-609
• Main Authors: Ana, Rasillo, Dolores, Tabernero María, Luz, Sánchez María, de Andrés Martín, Pérez, Marta, Martín Ayuso, José, Hernández, Jesús, Moro María, Javier, Fernández‐Calvo, María, Sayagués José, Aglae, Bortoluci, Fernando, San Miguel Jesús, Alberto, Orfao
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Aneuploidy; Biological and medical sciences; Chromosome Aberrations; chromosome numerical abnormalities; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 6; Chromosomes, Human, Pair 9; Female; Hematology; Humans; Immunophenotyping; In Situ Hybridization, Fluorescence; interphase fluorescence in situ hybridization (FISH); Investigative techniques, diagnostic techniques (general aspects); Leukemia, Plasma Cell - genetics; Leukemia, Plasma Cell - pathology; Male; Medical sciences; Middle Aged; monoclonal gammopathy of undetermined significance (MGUS); Multiple Myeloma - genetics; Multiple Myeloma - pathology; Paraproteinemias - genetics; Paraproteinemias - pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; plasma cell clones
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.11100

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)