Identification of New Nonrandom Translocations in Multiple Myeloma With Multicolor Spectral Karyotyping

Blood ◽  
1998 ◽  
Vol 92 (11) ◽  
pp. 4269-4278 ◽  
Author(s):  
Jeffrey R. Sawyer ◽  
Janet L. Lukacs ◽  
Nikhil Munshi ◽  
K. Raman Desikan ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
In Situ Hybridization ◽  
Chromosome Aberrations ◽  
Chromosome Morphology ◽  
Spectral Karyotyping ◽  
Chromosome Translocations ◽  
Igh Locus ◽  
Additional Chromosome

Multicolor spectral karyotyping (SKY) was performed on bone marrow samples from 50 patients with multiple myeloma (MM) in anticipation of discovering new previously unidentified translocations. All samples showed complex karyotypes with chromosome aberrations which, in most cases, were not fully characterized by G-banding. Patients of special interest were those who showed add(14)(q32), add(8)(q24) and those whose G-banding karyotypes showed poor chromosome morphology. Three new recurring chromosome translocations not previously reported in MM were identified. Two of the translocations involve recurring aberrations at band 14q32.3, the site of the IgH locus, with different exchange partners. The most frequently recurring rearrangement was a subtle translocation at 14q32.3 designated as a t(14;16)(q32;q22∼23), which was identified in six patients. A second and larger translocation at 14q32, identified in two patients, was designated as a t(9;14)(p13;q32), previously associated with Waldenstrom’s macroglobulinemia and lymphoplasmacytoid lymphoma. A third translocation, identified in two patients, involved a whole-arm t(6;8)(p10;q10) translocation. The SKY technique was able to refine the designations of over 156 aberrations not fully characterized by G-banding in this study and resolved additional chromosome aberrations in every patient studied except two. The t(14;16)(q32;q22∼23) identified by SKY in this study suggests this may be a frequent translocation in MM associated with complex karyotypes and disease progression. Therefore, the SKY technique provides a useful adjunct to routine G-banding and fluorescence in situ hybridization studies in the cytogenetic analysis of MM.

Identification of New Nonrandom Translocations in Multiple Myeloma With Multicolor Spectral Karyotyping

Blood ◽  
1998 ◽  
Vol 92 (11) ◽  
pp. 4269-4278 ◽  
Author(s):  
Jeffrey R. Sawyer ◽  
Janet L. Lukacs ◽  
Nikhil Munshi ◽  
K. Raman Desikan ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
In Situ Hybridization ◽  
Chromosome Aberrations ◽  
Chromosome Morphology ◽  
Spectral Karyotyping ◽  
Chromosome Translocations ◽  
Igh Locus ◽  
Additional Chromosome

Abstract Multicolor spectral karyotyping (SKY) was performed on bone marrow samples from 50 patients with multiple myeloma (MM) in anticipation of discovering new previously unidentified translocations. All samples showed complex karyotypes with chromosome aberrations which, in most cases, were not fully characterized by G-banding. Patients of special interest were those who showed add(14)(q32), add(8)(q24) and those whose G-banding karyotypes showed poor chromosome morphology. Three new recurring chromosome translocations not previously reported in MM were identified. Two of the translocations involve recurring aberrations at band 14q32.3, the site of the IgH locus, with different exchange partners. The most frequently recurring rearrangement was a subtle translocation at 14q32.3 designated as a t(14;16)(q32;q22∼23), which was identified in six patients. A second and larger translocation at 14q32, identified in two patients, was designated as a t(9;14)(p13;q32), previously associated with Waldenstrom’s macroglobulinemia and lymphoplasmacytoid lymphoma. A third translocation, identified in two patients, involved a whole-arm t(6;8)(p10;q10) translocation. The SKY technique was able to refine the designations of over 156 aberrations not fully characterized by G-banding in this study and resolved additional chromosome aberrations in every patient studied except two. The t(14;16)(q32;q22∼23) identified by SKY in this study suggests this may be a frequent translocation in MM associated with complex karyotypes and disease progression. Therefore, the SKY technique provides a useful adjunct to routine G-banding and fluorescence in situ hybridization studies in the cytogenetic analysis of MM.

Detection of t(4;14)(p16.3;q32) Chromosomal Translocation in Multiple Myeloma by Double-Color Fluorescent In Situ Hybridization

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 724-732 ◽  
Author(s):  
Palma Finelli ◽  
Sonia Fabris ◽  
Savina Zagano ◽  
Luca Baldini ◽  
Daniela Intini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Cell Lines ◽  
Fluorescent In Situ Hybridization ◽  
Chromosomal Translocation ◽  
Fish Analysis ◽  
Interphase Nuclei ◽  
Igh Locus ◽  
Normal Controls

Abstract Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus at chromosome 14q32 represent a common mechanism of oncogene activation in lymphoid malignancies. In multiple myeloma (MM), variable chromosome partners have been identified by conventional cytogenetics, including the 11q13, 8q24, 18q21, and 6p21 loci. We and others have recently reported a novel, karyotypically undetectable chromosomal translocation t(4;14)(p16.3;q32) in MM-derived cell lines, as well as in primary tumors. The 4p16.3 breakpoints are relatively scattered and located less than 100 kb centromeric of the fibroblast growth factor receptor 3 (FGFR3) gene or within the recently identified WHSC1 gene, both of which are apparently deregulated by the translocation. To assess the frequency of the t(4;14)(p16.3;q32) translocation in MM, we performed a double-color fluorescent in situ hybridization (FISH) analysis of interphase nuclei with differently labeled probes specific for the IGH locus (a pool of plasmid clones specific for the IGH constant regions) or 4p16.3 (yeast artificial chromosome (YAC) 764-H1 spanning the region involved in breakpoints). Thirty MM patients, the MM-derived cell lines KMS-11 and OPM2, and six normal controls were examined. The identification of a t(4;14) translocation, evaluated as the presence of a der(14) chromosome, was based on the colocalization of signals specific for the two probes; a cutoff value of 15% (mean + 3 standard deviation [SD]) derived from the interphase FISH of the normal controls (range, 5% to 11%; mean ± SD, 8.16 ± 2.2) was used for the quantification analysis. In interphase FISH, five patients (one in clinical stage I, two in stage II, one in stage III, and a plasma cell leukemia) were found to be positive (≈15%). FISH metaphases with split or colocalized signals were detected in only two of the translocated cases and confirmed the pattern found in the interphase nuclei. Furthermore, in three of the five cases with the translocation, FISH analysis with the IGH joining probe (JH) showed the presence of the reciprocal product of the translocation [der(4) chromosome]. Overall, our study indicates that the t(4;14)(p16.3;q32) chromosomal translocation is a recurrent event in MM tumors and may contribute towards the detection of this lesion and our understanding of its pathogenetic and clinical implications in MM.

Interphase Fluorescence In Situ Hybridization Detection of Cytogenetic Abnormalities in B-Cell Chronic Lymphocytic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4992-4992
Author(s):  
Wei Xu ◽  
Jianyong Li ◽  
Jinlan Pan ◽  
Li Li ◽  
Hairong Qiu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Situ Hybridization ◽  
B Cell ◽  
Fluorescence In Situ Hybridization ◽  
Peripheral Blood ◽  
Chromosome Aberrations ◽  
Lymphocytic Leukemia ◽  
Chromosome 12 ◽  
Molecular Cytogenetic

Abstract The most frequent chromosomal abnormalities in B-cell chronic lymphocytic leukaemia (B-CLL) are deletions on 13q14 and 17p13, trisomy 12 and 14q32 rearrangement. Conventional metaphase cytogenetic analysis underestimates the frequency of specific chromosome aberrations in B-CLL due to the low rate of spontaneous mitoses and poor response to mitogen stimulation. The aim of this study was to investigate the incidence of chromosomal changes in bone marrow or peripheral blood cells (or both) of B-CLL patients using a molecular cytogenetic method, interphase fluorescence in situ hybridization (I-FISH). Probes for 13q14 (D13S319), 17p13 (P53 gene), the centromere of chromosome 12 (D12Z3) and 14q32 (Ig10 and Y6) were applied to detect chromosomal aberrations on bone marrow and peripheral blood smears from 83 B-CLL patients (60 male, 23 female,). Molecular cytogenetic aberrations were found in 60 (72.3%) cases, and 8 (9.6%) patients showed two kinds of abnormalities. The most frequent abnormalities detected in our patients was deletions of 13q14 in 34 cases (41.0%), followed by trisomy of chromosome 12 in 16 patients (19.3%), deletions of 17p13 in 10 patients (12%) and 14q32 rearrangement in 8 patients (9.6%). Statistical analyses were performed to correlate the molecular cytogenetic findings with Binet stages. No apparent differences in distribution were noted for anomalies del(13q14), del(17p13), +12 or 14q32 rearrangement among patients with various Binet stages. FISH was found to be a more rapid, exact and sensitive technique for the analysis of chromosome aberrations in CLL. FISH could provide accurate information of molecular cytogenetics for CLL.

Detection of t(4;14)(p16.3;q32) Chromosomal Translocation in Multiple Myeloma by Double-Color Fluorescent In Situ Hybridization

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 724-732 ◽  
Author(s):  
Palma Finelli ◽  
Sonia Fabris ◽  
Savina Zagano ◽  
Luca Baldini ◽  
Daniela Intini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Cell Lines ◽  
Fluorescent In Situ Hybridization ◽  
Chromosomal Translocation ◽  
Fish Analysis ◽  
Interphase Nuclei ◽  
Igh Locus ◽  
Normal Controls

Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus at chromosome 14q32 represent a common mechanism of oncogene activation in lymphoid malignancies. In multiple myeloma (MM), variable chromosome partners have been identified by conventional cytogenetics, including the 11q13, 8q24, 18q21, and 6p21 loci. We and others have recently reported a novel, karyotypically undetectable chromosomal translocation t(4;14)(p16.3;q32) in MM-derived cell lines, as well as in primary tumors. The 4p16.3 breakpoints are relatively scattered and located less than 100 kb centromeric of the fibroblast growth factor receptor 3 (FGFR3) gene or within the recently identified WHSC1 gene, both of which are apparently deregulated by the translocation. To assess the frequency of the t(4;14)(p16.3;q32) translocation in MM, we performed a double-color fluorescent in situ hybridization (FISH) analysis of interphase nuclei with differently labeled probes specific for the IGH locus (a pool of plasmid clones specific for the IGH constant regions) or 4p16.3 (yeast artificial chromosome (YAC) 764-H1 spanning the region involved in breakpoints). Thirty MM patients, the MM-derived cell lines KMS-11 and OPM2, and six normal controls were examined. The identification of a t(4;14) translocation, evaluated as the presence of a der(14) chromosome, was based on the colocalization of signals specific for the two probes; a cutoff value of 15% (mean + 3 standard deviation [SD]) derived from the interphase FISH of the normal controls (range, 5% to 11%; mean ± SD, 8.16 ± 2.2) was used for the quantification analysis. In interphase FISH, five patients (one in clinical stage I, two in stage II, one in stage III, and a plasma cell leukemia) were found to be positive (≈15%). FISH metaphases with split or colocalized signals were detected in only two of the translocated cases and confirmed the pattern found in the interphase nuclei. Furthermore, in three of the five cases with the translocation, FISH analysis with the IGH joining probe (JH) showed the presence of the reciprocal product of the translocation [der(4) chromosome]. Overall, our study indicates that the t(4;14)(p16.3;q32) chromosomal translocation is a recurrent event in MM tumors and may contribute towards the detection of this lesion and our understanding of its pathogenetic and clinical implications in MM.

Frequent Clonal Evolution in Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3919-3919
Author(s):  
Sang Mee Hwang ◽  
Jungeun Choi ◽  
Sunhee Yim ◽  
Tae Young Kim ◽  
Chaja See ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Factors ◽  
In Situ Hybridization ◽  
Clonal Evolution ◽  
Chromosome 1 ◽  
Structural Abnormalities ◽  
Conventional Cytogenetics

Abstract Abstract 3919 Background: Multiple myeloma is a clonal bone marrow disease characterized by the neoplastic transformation of differentiated B cells. Various complex cytogenetic and molecular genetic aberrations are present that are important for prognostication and follow up investigation. We investigated the clonal evolution of multiple myeloma patients at relapse or at progression compared from the diagnosis by conventional cytogenetics, fluorescence in situ hybridization (FISH) and cytoplasmic immunoglobulin fluroscence in situ hybridization (cIg FISH). Methods: 35 patients diagnosed as multiple myeloma by bone marrow examination from January 2003 to March 2011 were included. Conventional cytogenetics were performed in all patients at diagnosis and at relapse or progression. FISH was performed in 24 patients with available specimen for at least 3 items including −13/del(13q), p53 deletion/del(17p), 1q21 gain, p16 deletion, IgH rearrangement, t(4;14) and t(14;16). The FISH results were confirmed with cytoplasmic immunoglobulin FISH specifically staining plasma cells. Results: Forty-nine percent of the patients had relapsed or progressed with additional clonal evolutions and they were detected by conventional cytogenetics. Numerical abnormalities were more frequent than structural abnormalities and structural abnormalities involving chromosome 1 was frequent. Thirty-five percent had developed −13/13q loss which is considered a poor prognostic factor. cIg-FISH found additional aberrations in 20% of the patients such as RB1 deletion, del(17p) and t(14;16). Conclusion: Conventional cytogenetics and cIG-FISH are both necessary in relapsed patient since clonal evolutions develop in many patients which may only be detected by one method. Full evaluation of cIg-FISH including non-poor prognostic factors may be considered since new clones evolve that can be a candidate of follow-up marker and since prognostic factors can change as treatment modality changes. Disclosures: No relevant conflicts of interest to declare.

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