Incidence of submicroscopic deletions vary according to disease entities and chromosomal translocations in hematologic malignancies: investigation by fluorescence in situ hybridization

Rearrangements within the chromosome 11q13 region are frequent in hematologic malignancies. 50% of 75% of mantle cell lymphomas (MCLs) carry a translocation t(11;14) (q13;q32). Using Southern blot analysis, a BCL1 breakpoint can be detected in approximately 50% of MCLs. It is not known whether other MCLs harbor also breakpoints at 11q13. Breakpoints in this region not involved in t(11;14), are detected in chronic lymphocytic leukemia and acute myeloid leukemia. To detect and localize breakpoints at 11q13 more accurately, we have developed fluorescence in situ hybridization using two probe sets of differently labeled cosmids, symmetrically localized at either side of the major translocation cluster of BCL1. These probes span a region of 450 to 750 kb. We applied this assay to a series of hematologic malignancies with 11q13 abnormalities identified by classical cytogenetics. All four samples with a t(11;14) (q13;q32) showed dissociation of the differently colored signals in metaphase and interphase cells, thereby indicating a chromosomal break in the region defined by the probe sets. The frequency of abnormal metaphase and interphase cells was comparable with that observed in any of the 13 malignancies with other chromosomal 11q13 abnormalities, indicating that these chromosomal breaks occurred outside the 450- to 750-kb region covered by the probes. One patient showed triplication and one patient showed monoallelic loss of this region. The current data show that double-color fluorescence in situ hybridization is a simple and reliable method for detection of the t(11;14)(q13;q32) in interphase cell nuclei and that is can be used to distinguish this translocation from other 11q13 rearrangements in hematologic malignancies.

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Fluorescence in situ hybridization analyses of hematologic malignancies reveal frequent cytogenetically unrecognized 12p rearrangements

Leukemia ◽

10.1038/sj.leu.2400929 ◽

1998 ◽

Vol 12 (3) ◽

pp. 390-400 ◽

Cited By ~ 35

Author(s):

P Andreasson ◽

B Johansson ◽

R Billström ◽

S Garwicz ◽

F Mitelman ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Hematologic Malignancies

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The role of fluorescence in situ hybridization (FISH) for monitoring hematologic malignancies with BCR/ABL or ETO/AML1 rearrangement: a comparative study with FISH and G-banding on 919 consecutive specimens of hematologic malignancies

Cancer Genetics and Cytogenetics ◽

10.1016/j.cancergencyto.2003.09.014 ◽

2004 ◽

Vol 152 (1) ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Dong Young Lee ◽

Han Ik Cho ◽

Yoon Hee Kang ◽

Sung Soo Yun ◽

Sun Yang Park ◽

...

Keyword(s):

In Situ Hybridization ◽

Comparative Study ◽

Fluorescence In Situ Hybridization ◽

Hematologic Malignancies

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Quality Assurance/Quality Control of Fluorescence in Situ Hybridization Tests in Hematologic Malignancies

OBM Genetics ◽

10.21926/obm.genet.1804038 ◽

2018 ◽

Vol 2 (4) ◽

pp. 1-1 ◽

Cited By ~ 1

Author(s):

Zhenya Tang ◽

◽

Jun Gu ◽

Guilin Tang ◽

L. Jeffrey Medeiros ◽

...

Keyword(s):

Quality Control ◽

Quality Assurance ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Hematologic Malignancies

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Fluorescence In Situ Hybridization Detected MRD and Chimerism in Patients with Hematologic Malignancies after allo-HSCT.

Blood ◽

10.1182/blood.v106.11.5214.5214 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5214-5214

Author(s):

Huiying Qiu ◽

Yongquan Xue ◽

Jinlan Jin ◽

De Pei Wu

Keyword(s):

Stem Cell ◽

In Situ Hybridization ◽

Stem Cell Transplantation ◽

Fluorescence In Situ Hybridization ◽

Cell Transplantation ◽

Residual Disease ◽

Hematologic Malignancies ◽

Host Cells ◽

Hematopoietic Stem

Abstract Objective Monitoring of minimal residual disease (MRD) and cellular chimerism in patients with hematopoietic malignancies after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods From May 2001 to June 2005, seventy four patients were received allo-HSCT. Including 50 Males and 24 females. 41 patients received sibling HLA-matched BMT, 7 patients received un-related BMT, 9 patients received Nonmyeloablative stem cell transplantation (NST), 14 patients received related haploidentical transplantation and 3 patients received allo-PBSCT. Among them, 45 patients were diagnosed with CML, 13 patients with AML, 14 patients with ALL, one patient with Multiple myeloma and one patient with malignant lymphoma. Chimerism and MRD were monitored using X and Y specific centromeric probes or gene probes for BCR/ABL, MLL and AML1/ETO by fluorescence in situ hybridization (FISH),1000 cells were analysised. Results Among 18 patients, received sex-matched transplant, we did not found the former chromosome rearrangements in 14 patients after transplantation, MRD were detected in 17% and 10% of cells in two patients, MRD were decreased from 10% to 1% of cells after the reduction of the dose of immunotherapy in one patient four month later, the patient was still in remission one year after transplantation. Another patient died of sever GVHD after the reduction of immunotherapy. 2 patients were found to have the former chromosomal rearrangement 1 and 4 month after transplantation respectively who did not achieve remission after chemotherapy and died 3 and 5 months respectively after transplantation. Over 99% donor chimerisms were found in 44 patients on day 25, donor cells were at a low level (96.2%~98.7) in 7 patients on day 25, and increased over 99% on day 180, they were in remission without relapse. The donor chimerisms decreased gradually in 6 patients, host cells were found over 20 cells, 3 patients showed cytogenetic or hematologic bone marrow relapse, two patients died of sever GVHD after the reduction of cyclosporine A, Over 99% donor chimerisms was achieved in one patient. Conclusion FISH could play a pivotal role in the detection of MRD and chimerism. It is helpful to the evaluation of graft and relapse, to the guide of implement of early immunotherapy.

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Fluorescence in situ hybridization analysis of whole-arm 7;12 translocations in hematologic malignancies

Genes Chromosomes and Cancer ◽

10.1002/gcc.2870140110 ◽

1995 ◽

Vol 14 (1) ◽

pp. 56-62 ◽

Cited By ~ 22

Author(s):

Bertil Johansson ◽

Kristina Arheden ◽

Mattias Höglund ◽

Annika Othzén ◽

Albert N. Békássy ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Hematologic Malignancies ◽

Hybridization Analysis

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Identification of new translocations involvingETV6 in hematologic malignancies by fluorescence in situ hybridization and spectral karyotyping

Genes Chromosomes and Cancer ◽

10.1002/gcc.1127 ◽

2001 ◽

Vol 31 (2) ◽

pp. 134-142 ◽

Cited By ~ 52

Author(s):

Mar�a D. Odero ◽

Katrin Carlson ◽

Mar�a J. Calasanz ◽

Idoya Lahortiga ◽

Vandana Chinwalla ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Hematologic Malignancies ◽

Spectral Karyotyping

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Molecular characterization of 12p abnormalities in hematologic malignancies: deletion of KIP1, rearrangement of TEL, and amplification of CCND2

Blood ◽

10.1182/blood.v87.1.324.bloodjournal871324 ◽

1996 ◽

Vol 87 (1) ◽

pp. 324-330 ◽

Cited By ~ 2

Author(s):

M Hoglund ◽

B Johansson ◽

J Pedersen-Bjergaard ◽

P Marynen ◽

F Mitelman

Keyword(s):

Cell Cycle ◽

In Situ Hybridization ◽

Tumor Suppressor ◽

Fluorescence In Situ Hybridization ◽

Hematologic Malignancies ◽

Suppressor Gene ◽

Detectable Change ◽

Structural Rearrangements

Twenty patients with hematologic malignancies with 12p abnormalities were investigated by fluorescence in situ hybridization (FISH) using probes mapped to specific regions in 12p. The initial analysis using the YAC 964c10 (D12S736) revealed that all four cases with cytogenetically identified del(12p) had lost one copy of this YAC and that submicroscopic deletions had occurred in 10 of the 16 neoplasms with other 12p abnormalities, ie, translocations, additions, and insertions. The deletions were partially mapped with cosmids localized to subregions of 12p. One copy of the gene for p27kip1 (KIP1), involved in cell cycle entrance, was found to be lost in all cases in which deletions could be detected by other probes and in one case with a translocation as the only detectable change. This implicates KIP1 as a possible tumor suppressor gene affected by del(12p). Four translocations with no apparent concomitant deletions were detected. All four breakpoints resulted in a split D12S736 signal. In two of these cases, we showed that TEL was disrupted as a result of a t(5;12)(q32–33;p12) and a t(12;22)(p12;q12), respectively. Two lymphoid neoplasm--one non-Hodgkin's lymphoma and one Burkitt's lymphoma--with 12p amplifications were detected. In both cases cyclin D2 (CCND2) was within the amplified region. Thus, cytogenetic abnormalities of 12p in hematologic malignancies result in at least three different molecular changes: deletions of KIP1, amplifications of CCND2, and structural rearrangements of TEL.

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Mature B-Cell Leukemias With More Than 55% Prolymphocytes

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-0305-mbclwm ◽

2003 ◽

Vol 127 (3) ◽

pp. 305-309

Author(s):

Shakil Merchant ◽

Ellen Schlette ◽

Warren Sanger ◽

Raymond Lai ◽

L. Jeffrey Medeiros

Keyword(s):

In Situ Hybridization ◽

B Cell ◽

Fluorescence In Situ Hybridization ◽

Cytogenetic Analysis ◽

Lymphocytic Leukemia ◽

Chromosomal Translocations ◽

Prolymphocytic Leukemia ◽

Conventional Cytogenetic Analysis ◽

Myc Gene

Abstract Context.—The molecular genetic events involved in the pathogenesis of mature B-cell leukemias with more than 55% prolymphocytes are not well characterized. We have encountered 2 such cases in which conventional cytogenetic analysis identified Burkitt lymphoma–type chromosomal translocations involving 8q24. Objective.—To assess these 2 cases for involvement of the c-myc gene using fluorescence in situ hybridization analysis with probes specific for the c-myc and immunoglobulin heavy-chain (IgH) genes. Results.—In both cases, conventional cytogenetic analysis demonstrated complex karyotypes, including chromosomal translocations involving 8q24. In case 1, a case of de novo prolymphocytic leukemia, the t(8;14)(q24;q32) was detected. In case 2, a case of chronic lymphocytic leukemia in prolymphocytoid transformation, the t(8;22)(q24;q11) was identified. Fluorescence in situ hybridization studies showed c-myc/IgH fusion signals in case 1, proving the presence of the t(8;14). Split c-myc signals without fusion to IgH were observed in case 2, proving c-myc gene rearrangement and consistent with the t(8;22). Conclusion.—These results suggest that c-myc gene alterations may be involved in the pathogenesis of a subset of mature B-cell leukemias with more than 55% prolymphocytes.

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Hypermetaphase fluorescence in situ hybridization for quantitative monitoring of Philadelphia chromosome-positive cells in patients with chronic myelogenous leukemia during treatment

Blood ◽

10.1182/blood.v86.6.2343.bloodjournal8662343 ◽

1995 ◽

Vol 86 (6) ◽

pp. 2343-2349 ◽

Cited By ~ 58

Author(s):

DC Seong ◽

HM Kantarjian ◽

JY Ro ◽

M Talpaz ◽

J Xu ◽

...

Keyword(s):

Bone Marrow ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Chronic Myelogenous Leukemia ◽

Philadelphia Chromosome ◽

Hematologic Malignancies ◽

Myelogenous Leukemia ◽

Original Diagnosis ◽

Philadelphia Chromosome Positive

Using Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) as a model, our aim has been to develop a molecular cytogenetic method of high resolution analysis for monitoring the frequency of cells with nonrandom chromosome rearrangements in the bone marrow of patients receiving treatment for hematologic malignancies. Long-term exposure (24 hours) of bone marrow cultures to colcemid (0.1 microgram/mL) maximized a high frequency of metaphase collection. Such preparations were subjected to fluorescence in situ hybridization (FISH) using a 5 Mb probe that overlapped the region of the translocation at chromosome 9q34. This detected the Ph translocation in the resultant large number of overly contracted chromosome spreads. The procedure was validated and verified by studying 70 double-blind marrow samples from patients in different stages of Ph+ CML and from patients with Ph- hematologic malignancies (controls). This hypermetaphase FISH (HMF) method clearly identified Ph+ metaphases and allowed the analysis of 500 hypermetaphases per sample in less than 1 hour after FISH. HMF (1) identified statistically significant differences between the frequencies of Ph+ cells in samples that differed by less than 4%; (2) resolved such differences among patient samples that were all judged 100% Ph+ by standard G-band cytogenetics (CG); (3) resulted in the reclassification of response status in 23% of the patients initially classified by CG; (4) recognized Ph+ cells in 16% of patients characterized as having a complete cytogenetic response and in one patient with an original diagnosis of Ph- CML; and in one patient with an original diagnosis of Ph- CML; and (5) was informative where insufficient metaphases were obtainable for analysis by CG. HMF appears to be uniquely suitable for monitoring the status of patients with CML receiving treatment. It should also be applicable for patients with any hematologic diseases where chromosomal alterations are known and appropriate FISH probes are available.

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