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Hyperdiploidy Is a Common Finding in Monoclonal Gammopathy of Undetermined Significance and Monosomy 13 Is Restricted to These Hyperdiploid Patients

Authors' Affiliations: ¹ Service des Maladies du Sang, Hôpital Huriez; ² Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre, Lille, France ³ Laboratoire d'Hématologie, CHU; ⁴ Service des Maladies du Sang, CHU, Angers, France; and ⁵ Service des Maladies du Sang, Hôtel Dieu, Nantes, France

Requests for reprints: Marc Zandecki, Laboratoire d'Hématologie, CHU, 4, rue Larrey, 49000 Angers, France. Fax: 33-2-41-35-55-99; E-mail: MaZandecki{at}chu-angers.fr.

Purpose: Two pathways, hyperdiploid and nonhyperdiploid, are proposed for progression to plasma cell neoplasia. Implication of monosomy 13 (13) is unclear in monoclonal gammopathy of undetermined significance (MGUS), and data on DNA content of plasma cells [DNA index (DI)] are rare.

Experimental Design: We ascertained DI in 169 multiple myeloma (MM) and 96 MGUS patients. Interphase fluorescence in situ hybridization (FISH) coupled to cytoplasmic staining of specific Ig (cIg-FISH) was done to look for trisomies and to ascertain 13.

Results: Hyperdiploidy and hypodiploidy were found in 54% and 11.5% of MGUS patients and in 59.5% and 25% of MM patients, respectively. In MGUS patients tested using probes for odd chromosomes, cIg-FISH showed association between trisomies for chromosomes 3, 7, 9, 11, or 15 and hyperdiploidy. 13 was found in 45.3% and 24.6% of MM and MGUS patients, respectively. Most 13 cases observed in MGUS were found within hyperdiploid clones, 38% versus 11% in hypodiploid cases, in sharp contrast with the occurrence of 13 in MM patients, 31.9% and 76.3%, respectively. That peculiar distribution of 13 according to DI persisted with other thresholds used to ascertain hyperdiploidy, such as DI 1.05. A strong relationship between IgA peak and hypodiploidy (P = 0.007) was only observed in MM, whereas light chain was significantly associated with hypodiploidy in MGUS (P = 0.001) and MM (P = 0.05). Hyperdiploidy shows similar pattern in MGUS and MM.

Conclusion: This fits well a hyperdiploid pathway leading to MM after a preceding MGUS stage. Yet-to-be-determined secondary event(s) needs to occur for the transition to MM, unrelated to changes in chromosome number or to loss of chromosome 13. In contrast, the "nonhyperdiploid" pathway needs to be clarified further because hypodiploidy is less common in MGUS than in MM and 13 is rare in hypodiploid MGUS patients compared with hypodiploid MM patients.