Deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy

Abstract

Deletions of the long arm of chromosome 13 (13q−) are observed in patients with multiple myeloma (MM), are rarely observed in the monoclonal gammopathy of undetermined significance (MGUS) and have been associated with a worsened prognosis in MM. However, no minimally deleted region in the13q arm has been defined at 13q, and consequently no tumor suppressor genes have yet been identified that are important for disease pathogenesis. We attempted to characterize these chromosome 13q deletions at the molecular cytogenetic level. We studied 351 newly diagnosed patients, entered into the E9486/E9487 clinical study of the Eastern Cooperative Oncology Group. Fluorescent in situ hybridization (FISH) combined with immune fluorescent detection (cIg-FISH) of clonal plasma cells (PC) and cytomorphology were used to analyze interphase, bone marrow (BM) cell, cytospin slides. We simultaneously used DNA probes for the following locus specific probes (LSI); LSI 13 (Rb) and D13S319, which hybridize to 13q14. We subsequently studied distal deletions using the D13S25 probe (13q14.3) and a subtelomeric probe (13qSTP) for the 13q-arm (D13S327) in 40 cases with documented LSI 13 (Rb)/D13S319 deletion and 40 without deletion of these loci. Of 325 evaluable patients, we found 13q deletions in 176 (54%) using LSI 13 (Rb) and D13S319 probes. Of 40 patients with LSI 13 (Rb)/D13S319 deletions, 34 (85%) had coexistent deletion of both D13S25/13qSTP. These results indicate that chromosome 13 deletions in MM involve loss of most if not all of the 13q arm perhaps even indicating monosomy. In six cases the 13qSTP signal was conserved, but D13S25 was lost indicating large interstitial deletions involving 13q14. In 39 of the 40 cases without LSI 13 (Rb)/D13S319 deletions, the normal pattern of two pairs of signals was observed for D13S25/13qSTP. Deletions involving 13q14 are very common in MM as detected by cIg-FISH. These deletions appear to predominantly involve loss of large segments of the 13q arm or monosomy 13, and only occasionally represent an interstitial deletion. Leukemia (2001) 15, 981-986.

A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy

“…21,22,24,28,39,44,55,56 At least five large studies in over 1500 patients treated with conventional therapy, single or tandem transplant, with or without thalidomide, have demonstrated a uniformly unfavorable prognosis for this group of patients as measured by gene expression, fluorescent in situ hybridization (FISH) or immunohistochemistry. 22,28,44,46,55,56 This patient population is also present in premalignant MGUS, but is more common in smoldering and active MM. The t(4;14) population is enriched in IgA isotype MM and in cohorts of patients with relapsed disease.…”

“…32,34,[65][66][67][68] However, the reported prevalence in MM is 50% when interphase FISH has been applied. [54][55][56][65][66][67][68][69][70] Independent of the mode of treatment (standard versus high-dose chemotherapy) and the mode of detection (karyotype versus FISH), MM cases with deletion 13 are associated with shorter survival and lower response rate to treatment. 32 The net effect of deletion 13 on prognosis is, however, greater when deletion 13 is detected by karyotype than when it is detected by interphase FISH.…”

Prognostic factors for hyperdiploid-myeloma: effects of chromosome 13 deletions and IgH translocations

“…Hybridization, validation and scoring procedures have been reported in detail in our previous studies. 8,12,16,17,26,27 …”

Detection of 13q deletion in multiple myeloma using immunomagnetically selected plasma cells

“…of MM patients' samples using FISH analysis, 4,5 which have been seen as a prognostic indicator of poor outcomes, 5,6 as well as increased serum levels of Creactive protein, lactate dehydrogenase and Durie & Salmon' stage III. 7 Herein, we present, for educational purposes, the description and the images obtained from a bone marrow sample analysed by FISH of a MM case with 13q14 deletion seen at the Haematology and Haemotherapy Centre of the State University of Campinas.…”