Characterization of Patients with Multiple Myeloma and t(4;14) Detected by Fluorescence In Situ Hybridization.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5092-5092
Author(s):  
Rosa Collado ◽  
Jose A. Hueso ◽  
Miriam Romaguera ◽  
Carmen Mora ◽  
Aurelio Lopez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Mean Value ◽  
Bone Lesions ◽  
Fish Analysis ◽  
Lytic Bone Lesions ◽  
Successful Technique

Abstract Multiple myeloma (MM) is a genetically unstable malignancy of postgerminal center B-cells. Almost 40% of intramedullary MM tumors show primary translocations that affect immunoglobulin heavy chain (IgH) gene. These include t(4;14)(p16;q32) which results in the dysregulated expression of two potential oncogenes, MMSET on der(4) and FGFR3 on der(14), and has been associated with poor outcome. The main goals of this study were to determine the incidence and clinical significance of t(4;14) among our MM patients. Therefore, we studied bone marrow specimens from 65 patients with MM by fluorescence in situ hybridization (FISH). All cases were screened for IgH rearrangements, t(4;14), t(11;14), and 13q14 deletions using the locus-specific probes LSI IgH dual color, break apart, LSI IGH/FGFR3, LSI IGH/CCND1, and LSI D13S319 (Vysis). FISH analysis revealed 35 cases (54%) involving IgH locus. 8 patients (12.3%) had a t(4;14), and 13 cases (20%) showed a t(11;14). In the remaining 14 samples (21.5%), IgH rearrangements were observed, but the translocation partner was not one of the loci for we tested. Furthermore, 13q14 deletions were more frequent among patients with t(4;14) than among those with t(11;14) (62.5% vs 30.7% respectively, p=0.03). Regarding clinical parameters, presence of t(4;14) was significantly associated with anemia (mean value: 9.0 g/dl, p=0.049), elevated LDH levels (mean value: 535.4 U/l, p=0.05), Durie III stage (p=0.049), and number of lytic bone lesions >2 (p=0.007). Finally, the survival median of patients with t(4;14) was 23 months vs 48 months for the group without this abnormality. Cases with t(11;14) did not show adverse correlation with survival. Based on these data, FISH is a successful technique to detect translocations affecting telomeric localization of both chromosomal partner loci. In addition, we confirmed t(4;14) as an important factor of poor prognostic in MM. Its detection is essential to lead a correct evaluation of patients at diagnosis.

Different mechanisms of cyclin D1 overexpression in multiple myeloma revealed by fluorescence in situ hybridization and quantitative analysis of mRNA levels

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 1120-1126 ◽  
Author(s):  
Katja Specht ◽  
Eugenia Haralambieva ◽  
Karin Bink ◽  
Marcus Kremer ◽  
Sonja Mandl-Weber ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Cyclin D1 ◽  
Gene Dosage ◽  
Fish Analysis ◽  
Alternative Mechanism ◽  
Mrna Levels ◽  
Chromosome 11

AbstractThe t(11;14)(q13;q32) is the most common translocation in multiple myeloma (MM), resulting in up-regulation of cyclin D1. We used a segregation fluorescence in situ hybridization (FISH) assay to detect t(11;14) breakpoints in primary MM cases and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify cyclin D1 and MYEOV (myeloma overexpressed) expression, another putative oncogene located on chromosome 11q13. High levels of cyclin D1 mRNA (cyclin D1/TBP [TATA box binding protein] ratio > 95) were found exclusively in the presence of a t(11;14) translocation (11/48 cases; P < .00001). In addition, a subgroup of MM cases (15/48) with intermediate to low cyclin D1 mRNA (cyclin D1/TBP ratio between 2.3 and 20) was identified. FISH analysis ruled out a t(11; 14) translocation and 11q13 amplification in these cases; however, in 13 of 15 patients a chromosome 11 polysomy was demonstrated (P < .0001). These results indicate an effect of gene dosage as an alternative mechanism of cyclin D1 deregulation in MM. The absence of chromosome 11 abnormalities in 2 of 15 patients with intermediate cyclin D1 expression supports that there are presumably other mechanism(s) of cyclin D1 deregulation in MM patients. Our data indicate that deregulation of MYEOV is not favored in MM and further strengthens the role of cyclin D1 overexpression in lymphoid malignancies with a t(11;14)(q13;q32) translocation. (Blood. 2004;104:1120-1126)

scholarly journals Mate pair sequencing outperforms fluorescence in situ hybridization in the genomic characterization of multiple myeloma

2019 ◽  
Vol 9 (12) ◽  
Author(s):  
James Smadbeck ◽  
Jess F. Peterson ◽  
Kathryn E. Pearce ◽  
Beth A. Pitel ◽  
Andrea Lebron Figueroa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Position Effect ◽  
False Negative ◽  
Prognostic Significance ◽  
Plasma Cell Dyscrasia ◽  
Mate Pair

AbstractFluorescence in situ hybridization (FISH) is currently the gold-standard assay to detect recurrent genomic abnormalities of prognostic significance in multiple myeloma (MM). Since most translocations in MM involve a position effect with heterogeneous breakpoints, we hypothesize that FISH has the potential to miss translocations involving these regions. We evaluated 70 bone marrow samples from patients with plasma cell dyscrasia by FISH and whole-genome mate-pair sequencing (MPseq). Thirty cases (42.9%) displayed at least one instance of discordance between FISH and MPseq for each primary and secondary abnormality evaluated. Nine cases had abnormalities detected by FISH that went undetected by MPseq including 6 tetraploid clones and three cases with missed copy number abnormalities. In contrast, 19 cases had abnormalities detected by MPseq that went undetected by FISH. Seventeen were MYC rearrangements and two were 17p deletions. MPseq identified 36 MYC abnormalities and 17 (50.0% of MYC abnormal group with FISH results) displayed a false negative FISH result. MPseq identified 10 cases (14.3%) with IgL rearrangements, a recent marker of poor outcome, and 10% with abnormalities in genes associated with lenalidomide response or resistance. In summary, MPseq was superior in the characterization of rearrangement complexity and identification of secondary abnormalities demonstrating increased clinical value compared to FISH.

Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization

Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 1925-1930 ◽  
Author(s):  
Niklas Zojer ◽  
Robert Königsberg ◽  
Jutta Ackermann ◽  
Elke Fritz ◽  
Susanne Dallinger ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Plasma Cells ◽  
Clinical Importance ◽  
Myeloma Cell ◽  
Fish Analysis ◽  
Newly Diagnosed ◽  
Ki 67

Abstract Interphase fluorescence in situ hybridization (FISH) studies of chromosomal region 13q14 were performed to investigate the incidence and clinical importance of deletions in multiple myeloma (MM). Monoallelic deletions of the retinoblastoma-1 (rb-1) gene and the D13S319 locus were observed in 48 of 104 patients (46.2%) and in 28 of 72 (38.9%) patients, respectively, with newly diagnosed MM. FISH studies found that 13q14 was deleted in all 17 patients with karyotypic evidence of monosomy 13 or deletion of 13q but also in 9 of 19 patients with apparently normal karyotypes. Patients with a 13q14 deletion were more likely to have stage III disease (P = .022), higher serum levels of β2-microglobulin (P = .059), and a higher percentage of bone marrow plasma cells (P = .085) than patients with a normal 13q14 status on FISH analysis. In patients with a deletion of 13q14, myeloma cell proliferation (Ki-67) was markedly increased (22.0% ± 6.9% compared with 15.6% ± 8.2% in patients without the deletion;P = .0008). Evaluation of bromodeoxyuridine incorporation in 5 patients revealed that both rb-1–deleted and rb-1–normal MM subpopulations were proliferative. The presence of a 13q14 deletion on FISH analysis was associated with a significantly lower rate of response to conventional-dose chemotherapy (40.8% compared with 78.6%; P = .009) and a shorter overall survival (24.2 months compared with > 60 months; P < .005) than in patients without the deletion. Multivariate analysis of prognostic factors confirmed the independent predictive value of 13q14 deletions for shortened survival. In conclusion, deletions of 13q14 are frequently detected by interphase FISH in patients with newly diagnosed MM, correlate with increased proliferative activity, and represent an independent adverse prognostic feature in MM.

scholarly journals An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Kosuke Miki ◽  
Naoshi Obara ◽  
Kenichi Makishima ◽  
Tatsuhiro Sakamoto ◽  
Manabu Kusakabe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Plasma Cells ◽  
Bone Marrow Examination ◽  
Bone Lesions ◽  
Dexamethasone Treatment ◽  
Lytic Bone Lesions

We report the case of a 76-year-old man who was diagnosed as having chronic myeloid leukemia (CML) with p190 BCR-ABL while receiving treatment for symptomatic multiple myeloma (MM). The diagnosis of MM was based on the presence of serum M-protein, abnormal plasma cells in the bone marrow, and lytic bone lesions. The patient achieved a partial response to lenalidomide and dexamethasone treatment. However, 2 years after the diagnosis of MM, the patient developed leukocytosis with granulocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed Philadelphia chromosomes and chimeric p190 BCR-ABL mRNA. Fluorescence in situ hybridization also revealed BCR-ABL-positive neutrophils in the peripheral blood, which suggested the emergence of CML with p190 BCR-ABL. The codevelopment of MM and CML is very rare, and this is the first report describing p190 BCR-ABL-type CML coexisting with MM. Moreover, we have reviewed the literature regarding the coexistence of these diseases.

Molecular Cytogenetic Characterization of the DiGeorge Syndrome Region Using Fluorescence in Situ Hybridization

Genomics ◽  
1993 ◽  
Vol 17 (2) ◽  
pp. 403-407 ◽  
Author(s):  
Elizabeth A. Lindsay ◽  
Stephanie Halford ◽  
Roy Wadey ◽  
Peter J. Scambler ◽  
Antonio Baldini
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Digeorge Syndrome ◽  
Molecular Cytogenetic ◽  
Cytogenetic Characterization

scholarly journals Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4696-4700 ◽  
Author(s):  
Nikhil C. Munshi ◽  
Kenneth C. Anderson ◽  
P. Leif Bergsagel ◽  
John Shaughnessy ◽  
Antonio Palumbo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
High Risk ◽  
Risk Stratification ◽  
Fluorescence In Situ Hybridization ◽  
High Serum ◽  
Β2 Microglobulin ◽  
Poor Outcome ◽  
13Q Deletion

Abstract A panel of members of the 2009 International Myeloma Workshop developed guidelines for risk stratification in multiple myeloma. The purpose of risk stratification is not to decide time of therapy but to prognosticate. There is general consensus that risk stratification is applicable to newly diagnosed patients; however, some genetic abnormalities characteristic of poor outcome at diagnosis may suggest poor outcome if only detected at the time of relapse. Thus, in good-risk patients, it is necessary to evaluate for high-risk features at relapse. Although detection of any cytogenetic abnormality is considered to suggest higher-risk disease, the specific abnormalities considered as poor risk are cytogenetically detected chromosomal 13 or 13q deletion, t(4;14) and del17p, and detection by fluorescence in situ hybridization of t(4;14), t(14;16), and del17p. Detection of 13q deletion by fluorescence in situ hybridization only, in absence of other abnormalities, is not considered a high-risk feature. High serum β2-microglobulin level and International Staging System stages II and III, incorporating high β2-microglobulin and low albumin, are considered to predict higher risk disease. There was a consensus that the high-risk features will change in the future, with introduction of other new agents or possibly new combinations.

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