Vergleichende genomische Hybridisierung (CGH) zur Aufklärung genomischer Imbalancen bei hämatologischen Neoplasien mit Chromosomensätzen über 50 Elemente
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Philipps-Universität Marburg
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Abstract
We used comparative genomic hybridization to
study the chromosomal status of 20 adult patients with
haematological malignancies (16 ALL, 2 AML and 2 NHL). In 8
cases CGH was performed with DNA recovered from fixed cells by
the use of chelating resins and universally amplified by
DOP-PCR. The results did not differ from those performed with
conventionally prepared DNA if normal genomic DNA that had also
undergone DOP-PCR was used as reference sample. The childhood
ALL > 50 chromosomes is associated with a favorable
prognosis. No such favorable prognosis can be identified in
adult ALL > 50. A certain pattern of chromosome gains und
losses has been described in ALL > 50. In this study the
hyperdiploid cases did have the same distribution of gained
chromosomes as described in childhood ALL (4, 6, 10, 14, 17,
18, 21, X). So the difference in prognosis may be not explained
by a different chromosome pattern. Structural chromosomal
abnormalities in general are associated with a poor treatment
outcome. The combination of CGH und conventional karyotyping
provides more precise information about structural chromosomal
abnormalities than conventional cytogenetics alone. In the
combined analysis we found that the amount of structural
chromosomal abnormalities in our adult patients with ALL >
50 was higher than the amount described in children. This
result may explain the difference in treatment outcome between
children and adults with ALL > 50. The CGH revealed losses
at 9p which were not detected by cytogenetic analysis. At
2q21q31, 3q24q26 and 13q21q32 partial gains were detected,
possibly nonrandom abnormalities in adult ALL > 50. In a
case with tetraploid karyotype CGH found an isochromosome 17q,
that possibly indicates the formation of the tetraploid
karyotype by loss of tumor suppressor gene TP53 and following
duplication of the karyotype. In the two cases of NHL CGH found
gains of chromosomal material on 1q, 3q, 8q, 13q and 18q and
losses of 17q, imbalances that are known to be associated with
tumor progression and clinical outcome. At Xq28 CGH detected a
gain of chromosomal material in a region where a
lymphoma-associated oncogene may exist. In one case of
tetraploid AML CGH revealed an isochromosome 8q and loss of 5q,
both are markers of secondary acute myeloid
leukemia.
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Dates
Created: 2003Issued: 2004-04-01Updated: 2011-08-10
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
DOP-PCR, ALL des Erwachsenen , HyperdiploidComparative genomic hybridizationVergleichende genomische HybridisierungCGHCGHAMLALLNHL
DFG-subjects
Akute myeloische LeukämieNon-Hodgkin-Lymphom , Fluoreszenz-in-situ-HybridisierungCytogenetik , CarcinoAkute lymphatische Leukämie
DDC-Numbers
610
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Teichgraeber, Achim (128939915): Vergleichende genomische Hybridisierung (CGH) zur Aufklärung genomischer Imbalancen bei hämatologischen Neoplasien mit Chromosomensätzen über 50 Elemente. : Philipps-Universität Marburg 2004-04-01. DOI: https://doi.org/10.17192/z2004.0212.
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This item has been published with the following license: In Copyright