Low‐depth sequencing for copy number abnormalities in multiple myeloma supersedes fluorescent in situ hybridization in scope and resolution

2019 ◽  
Vol 96 (2) ◽  
pp. 163-168 ◽  
Author(s):  
Manal O. Elnenaei ◽  
Philipp Knopf ◽  
Samuel D. Cutler ◽  
Keaton Sinclair ◽  
Mohamed Abou El Hassan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Copy Number ◽  
Fluorescent In Situ Hybridization

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.

Fluorescent in situ hybridization assessment of chromosomes 1 and 17 copy number in neoplastic and normal tissues of cancer-associated breasts

The Breast ◽  
1997 ◽  
Vol 6 (5) ◽  
pp. 324-325
Author(s):  
C. Botti ◽  
R. Bovani ◽  
C. Greco ◽  
F. Cavaliere ◽  
M. Benevolo ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Copy Number ◽  
Fluorescent In Situ Hybridization ◽  
Normal Tissues

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.

Assessment of Chromosome 8 Copy Number in Cervical Cancer by Fluorescent in situ Hybridization

1999 ◽  
Vol 66 (2) ◽  
pp. 157-162 ◽  
Author(s):  
H.F.L. Mark ◽  
D. Feldman ◽  
M. Samy ◽  
C.-L. Sun ◽  
Sam Das ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
In Situ Hybridization ◽  
Copy Number ◽  
Fluorescent In Situ Hybridization ◽  
Chromosome 8

Single Institution Study of Abnormalities Involving Chromosomes 13 and 17 Detected by Classical Cytogenetics and Fluorescent In Situ Hybridization in Myeloma and Their Relationship to Survival in Patients Undergoing Autologous Stem Cell Transplant.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5072-5072
Author(s):  
Arun Rajan ◽  
Constance Stein ◽  
Teresa Gentile ◽  
Chirag Shah
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
In Situ Hybridization ◽  
Fluorescent In Situ Hybridization ◽  
Single Institution ◽  
Conventional Cytogenetics ◽  
Normal Fish ◽  
Normal Cytogenetics ◽  
Classical Cytogenetics

Abstract Multiple myeloma is associated with a variety of chromosomal anomalies each of which may affect survival to varying degrees. Recent data indicate that patients with chromosome 13 and 17 anomalies have a poor prognosis. In the current single institution study we analyzed the presence of anomalies involving chromosomes 13 and 17 detected by classical cytogenetics (karyotype analysis) (CC) and interphase fluorescent in situ hybridization (FISH) in patients who underwent autologous stem cell transplantation for multiple myeloma and correlated this with mean survival. Our patients had undergone autologous stem cell transplantation between April 1998 and March 2006. Of the 79 patients studied, data on CC and FISH was available on 43 patients and 29 patients respectively. 34 of 43 patients had normal CC and 11 of 29 patients had normal FISH. The mean survival of patients with normal cytogenetics was 45.36 months and for those with a normal FISH result it was 50 months. 9 of 43 patients had an abnormal CC result and 18 of 29 patients had an abnormal FISH result. Mean survival with an abnormal CC result was 30.40 months compared to 40.83 months with an abnormal FISH result. Anomalies of chromosomes 13 and/or 17 were seen in 6 of 9 patients by CC and 15 of 18 patients by FISH. Mean survival in these two groups was 30.25 months and 42.80 months respectively. These results indicate that normal cytogenetics and fluorescent in situ hybridization results at the time of diagnosis are associated with favorable outcome. The presence of abnormalities detected by conventional cytogenetics is associated with poorer outcome, particularly for deletion 13q and deletion 17p. Patients with interphase FISH abnormalities for chromosomes 13 and 17 have better survival than those with abnormalities for these chromosomes detected by conventional cytogenetics. Abnormalities in conventional cytogenetics may suggest actively proliferating disease. Thus interphase FISH should not substitute for conventional cytogenetic analysis in the diagnosis of myeloma.

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