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Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2583-2589
Monosomy 13 Is Associated With the Transition of Monoclonal
Gammopathy of Undetermined Significance to Multiple Myeloma
Hervé Avet-Loiseau,
Jian-Yong Li,
Nadine Morineau,
Thierry Facon,
Christophe Brigaudeau,
Jean-Luc Harousseau,
Bernard Grosbois, and
Régis Bataille on behalf of the Intergroupe Francophone du
Myélome
From the Laboratory of Hematology, the Clinical Hematology
Department, Centre Hospitalier Universitaire, Nantes, France; the
Service des Maladies du Sang, Centre Hospitalier Universitaire, Lille,
France; the Laboratory of Hematology, Centre Hospitalier Universitaire,
Limoges, France; and the Service of Internal Medicine, Centre
Hospitalier Universitaire, Rennes, France.
Chromosomal abnormalities are present in most (if not all) patients
with multiple myeloma (MM) and primary plasma cell leukemia (PCL).
Furthermore, recent data have shown that numerical chromosomal changes
are present in most individuals with monoclonal gammopathy of
undetermined significance (MGUS). Epidemiological studies have shown
that up to one third of MM may emerge from pre-existing MGUS. To
clarify further possible stepwise chromosomal aberrations on a pathway
between MGUS and MM, we have analyzed 158 patients with either MM or
primary PCL and 19 individuals with MGUS using fluorescence in situ
hybridization (FISH). Our FISH analyses were designed to detect
illegitimate IGH rearrangements at 14q32 or monosomy 13. Whereas translocations involving the 14q32 region were observed with a
similar incidence (60%) in both conditions, a significant difference
was found in the incidence of monosomy 13 in MGUS versus MM or primary
PCL. It was present in 40% of MM/PCL patients, but in only 4 of 19 MGUS individuals. Moreover, whereas monosomy 13 was found in the
majority of plasma cells in MM, it was observed only in cell
subpopulations in MGUS. It is noteworthy that, in a group of 20 patients with MM and a previous MGUS history, incidence of monosomy 13 was 70% versus 31% in MM patients without a known history of MGUS
(P = .002). Thus, this study highlights monosomy 13 as
correlated with the transformation of MGUS to overt MM and may define 2 groups of MM with possible different natural history and outcome, ie,
post-MGUS MM with a very high incidence of monosomy 13 and de novo MM
in which other genetic events might be involved. Serial analyses of
individuals with MGUS will be needed to validate this model.
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