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  • Title: Long-term follow up with conventional cytogenetics and band 13q14 interphase/metaphase in situ hybridization monitoring in monoclonal gammopathies of undetermined significance.
    Author: Bernasconi P, Cavigliano PM, Boni M, Astori C, Calatroni S, Giardini I, Rocca B, Caresana M, Crosetto N, Lazzarino M, Bernasconi C.
    Journal: Br J Haematol; 2002 Aug; 118(2):545-9. PubMed ID: 12139743.
    Abstract:
    One-third of patients with monoclonal gammopathy of undetermined significance (MGUS) may progress to multiple myeloma (MM) and may develop a long arm deletion of chromosome 13 (13q-). As the incidence of 13q-, time of development and prognostic impact in MGUS patients is still under debate, we decided to perform serial sequential conventional cytogenetics (CC) and metaphase/interphase fluorescence in situ hybridization (FISH) analyses on bone marrow mononuclear cells obtained from 18 asymptomatic, untreated MGUS patients. Median follow up was 30 months (range 6-72). Interphase FISH identified a 13q14 deletion in five out of 18 patients (on clinical diagnosis in one patient and during the follow up in the remaining four patients). Subsequently, metaphase FISH and CC also identified the deletion in four out of five patients. All five of the patients progressed to MM 6-12 months after 13q- identification, without developing any FISH determined JH rearrangements. MM progression also occurred in two other karyotypically normal patients. We conclude that: (i) the extent of the 13q deletion does not vary during the clinical outcome; (ii)13q- plays a crucial role in MGUS/MM pathogenesis and confers a proliferative advantage to clonal plasma cells being initially demonstrated by interphase FISH and only afterwards by metaphase FISH and CC; and (iii) association of 13q- with t(4;14)(p16.3;q32) remains to be demonstrated. However, a transition from MGUS to MM may also occur in patients with normal karyotypes or other abnormalities, suggesting the possibility of distinct pathogenetic pathways.
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