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.

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.

scholarly journals Pattern of Cytogenetic Abnormality by Fluorescence in Situ Hybridization (FISH) in Multiple Myeloma Patients in a Tertiary Hospital

2022 ◽  
Vol 8 (1) ◽  
pp. 212-224
Author(s):  
Alamgir Ahmed
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Risk Stratification ◽  
Fluorescence In Situ Hybridization ◽  
Prognostic Significance ◽  
Staging System ◽  
Cytogenetic Abnormality ◽  
Survival Duration ◽  
Female Ratio

Background: Multiple myeloma is a plasma cell neoplasm with acquired genetic abnormalities of clinical and prognostic importance, with survival duration ranging from a few months to more than 10 years. Cytogenetic abnormalities (CA) detected by fluorescence in situ hybridization (FISH) are of major prognostic significance since e.g. patients with del(17p), t(4;14) or gain 1q21 show dismal outcome. Objective: To evaluate the cytogenetic patterns by fluorescence in situ hybridization (FISH) of clinically diagnosed cases of multiple myeloma.Methods:This cross-sectional study was conducted in Department of Haematology, Dhaka Medical College Hospital, Dhaka, from January 2018 to December 2018. A total number of 30 patients with multiple myeloma were analyzed cytogenetically by interphase fluorescence in situ hybridization (iFISH). The collected data were analyzed by using the Statistical Package for Social Science (SPSS-24) for windows version 10.0.Results:Out of 30 diagnosed Multiple Myeloma cases the mean age was 56.37±10.38 years and male to female ratio was almost 3:1. Sixteen (56.7%) of 30 patients. Among 30 cases of 8 cases were thyrogenicity positive of 7(23.3%) patients was detected del 13q positive. Isolated del 13q was found in 4 cases. 2 cases were found coexistence of del 13q and del 17p positive ;1 case was found coexistence of del 13q and t(4;14) positive and rest of 1 case had del 17 p positive. There was no detectable t (11; 14) and t(14;16) in any of 30 cases.Conclusion:FISH panel for Multiple Myeloma including del (13q); t(11;14); t(4;14), del(17p), t(14;16) is very important molecular test for the prognosis , risk stratification, treatment modality of the patient. On the basis of cytogenetic abnormality Multiple Myeloma risk stratification is modified now a day. This Revised International Staging system R-ISS is a simple and powerful prognostic staging system.

Frequent Gains of Chromosome Arm 1q21 in Plasma Cell Dyscrasia Detected by Fluorescence In Situ Hybridization: Incidence Increases from MGUS to Relapsed Myeloma and Is Related to Disease Progression and Prognosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1553-1553
Author(s):  
Ichiro Hanamura ◽  
Peter Stewart ◽  
Frederica Cavallo ◽  
Bart Burington ◽  
Erik Rasmussen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Disease Progression ◽  
Standard Of Care ◽  
Recurrent Event ◽  
Plasma Cell Dyscrasia ◽  
High Dose

Abstract Background: High-dose therapy with autologous stem cell transplantation (HDT-ASCT), effecting complete remissions in > 40% with median overall survival exceeding 6 years, has become the standard of care for patients with multiple myeloma (MM). Poor outcome following HDT-ASCT has been linked most strongly to metaphase cytogenetic abnormalities (CA). Tandem duplications and jumping translocations of the chromosome 1q21 region is a recurrent event in advanced MM and 1q21 amplification (amp1q21) and high expression of the CKS1B gene (mapping to 1q21), both signify poor survival in MM treated with HDT-ASCT. Smoldering multiple myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) have many of the genetic hallmarks of overt MM, but especially MGUS rarely proceeds to MM requiring treatment. The aim of this study was determine if amp1q21 relates to disease progression and prognosis. Patients and Methods: 467 untreated patients with MGUS (n = 14), SMM (n = 32) and MM (n = 421) as well as 42 with relapsed MM were examined by means of triple color interphase fluorescence in situ hybridization (TRI-FISH) of the CKS1B locus. Results: The frequency of ampq21 was 0% in 14 patients with MGUS, 43% in 32 with SMM, 43% in 421 with newly diagnosed MM and 78% in 42 with relapsed MM (p<0.001; untreated vs relapsed MM). Among SMM patients, 11 of 14 (78%) with amp1q21 but only 2 of 18 (11%) without amp1q21 progressed to active MM (p<0.001) (median follow-up, 44 mo; range, 0–120 mo). In 421 MM patients treated on Total Therapy 2 (high-dose melphalan-based tandem autotransplants +/− thalidomide), 5-yr overall survival/event-free survival were 75%/61% in without amp1q21 compared to 48%/34% with amp1q21 (both p<0.001). Among 42 relapses, amp1q21 was present in 20/21 occurring on thalidomide vs 13/21 on no thalidomide (p=0.020); the median post-relapse survival in those with amp1q21 was only 11 mo vs 25 mo in patients without amp1q21 (p=0.02). Conclusion: (1) Amp1q21 was absent in MGUS and present in >40% of symptomatic MM and SMM. (2) in SMM, amp1q21 was associated with a higher risk of conversion to MM. (3) In overt MM, amp1q21 conferred inferior event-free and overall survival.

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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