Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones

During fluorescence in situ hybridization (FISH) analysis of metaphase cells from 70 patients with lymphoid and myeloid hematologic malignancies and chromosomal rearrangements involving band 12p13, we identified nine patients (four with lymphoid malignancies, four with myeloid malignancies and one w...

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Veröffentlicht in:Leukemia 2001-08, Vol.15 (8), p.1193-1202
Hauptverfasser: SATO, Y, KOBAYASHI, H, SUTO, Y, OLNEY, H. J, DAVIS, E. M, GILL SUPER, H, ESPINOSA III, R, LE BEAU, M. M, ROWLEY, J. D
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container_end_page 1202
container_issue 8
container_start_page 1193
container_title Leukemia
container_volume 15
creator SATO, Y
KOBAYASHI, H
SUTO, Y
OLNEY, H. J
DAVIS, E. M
GILL SUPER, H
ESPINOSA III, R
LE BEAU, M. M
ROWLEY, J. D
description During fluorescence in situ hybridization (FISH) analysis of metaphase cells from 70 patients with lymphoid and myeloid hematologic malignancies and chromosomal rearrangements involving band 12p13, we identified nine patients (four with lymphoid malignancies, four with myeloid malignancies and one with biphenotypic leukemia) who showed more complicated rearrangements than we had expected from conventional cytogenetic study. In six patients, multiple breaks occurred in small segments of 12p with subsequent translocations and insertions of these segments into other chromosomes, sometimes to unexpected regions. In three patients additional chromosome breaks resulted in a sub-clone which was cytogenetically indistinguishable from the main clone in each patient based on the cytogenetic analysis. These subtle molecular events were detected exclusively in a region covering TEL/ETV6 and KIP1/CDKN1B. Seven of nine had a previous history of chemo/radiotherapy; all the patients showed complex karyotypes, even though they were newly diagnosed with leukemia. Survival data were available in five patients, and all survived less than 6 months. These findings suggest that the 12p13 region, especially the above-mentioned region, is genetically unstable and fragile. It is likely that multiple chromosome breaks were induced through mutagens used in chemo/ radiotherapy, and are associated with a sub-group of patients with an extremely bad prognosis.
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In three patients additional chromosome breaks resulted in a sub-clone which was cytogenetically indistinguishable from the main clone in each patient based on the cytogenetic analysis. These subtle molecular events were detected exclusively in a region covering TEL/ETV6 and KIP1/CDKN1B. Seven of nine had a previous history of chemo/radiotherapy; all the patients showed complex karyotypes, even though they were newly diagnosed with leukemia. Survival data were available in five patients, and all survived less than 6 months. These findings suggest that the 12p13 region, especially the above-mentioned region, is genetically unstable and fragile. 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subjects Biological and medical sciences
Blood cancer
Cancer
Care and treatment
chromosome 12
Chromosome banding
Chromosome Fragility
Chromosome rearrangements
Chromosome translocations
Chromosomes
Chromosomes, Human, Pair 12
Cloning
Cyclin-dependent kinase inhibitor p27
Cytogenetics
Fluorescence
Fluorescence in situ hybridization
Gene Rearrangement
Genetic aspects
Genomic instability
Hematologic and hematopoietic diseases
Hematologic Neoplasms - genetics
Hematology
Humans
In situ hybridization
Karyotypes
Kinases
KIP1/CDKN1 gene
Leukemia
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical prognosis
Medical sciences
Metaphase
Mutagens
Oncology
Patients
Radiation therapy
Segments
TEL/ETV6 gene
Transcription factors
title Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones
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