Frequent clonal loss of heterozygosity but scarcity of microsatellite instability at chromosomal breakpoint cluster regions in adult leukemias.

Details

Serval ID
serval:BIB_6DCED4AEBA6C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Frequent clonal loss of heterozygosity but scarcity of microsatellite instability at chromosomal breakpoint cluster regions in adult leukemias.
Journal
Blood
Author(s)
Pabst T., Schwaller J., Bellomo M.J., Oestreicher M., Mühlematter D., Tichelli A., Tobler A., Fey M.F.
ISSN
0006-4971
Publication state
Published
Issued date
1996
Volume
88
Number
3
Pages
1026-1034
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
Microsatellites are important highly polymorphic genetic markers dispersed in the human genome. Using a panel of 22 (CA)n repeat microsatellite markers mapped to recurrent breakpoint cluster regions specifically involved in leukemia, we investigated 114 adult leukemias (25 acute lymphocytic leukemia [ALL], 32 acute myeloid leukemia [AML], 36 chronic lymphocytic leukemia [CLL], and 21 chronic myeloid leukemia [CML] in chronic phase) for somatic mutations at these loci. In each patient, DNA from fresh leukemia samples was analyzed alongside normal constitutive DNA from buccal epithelium. We detected loss of heterozygosity (LOH) in 81 of 114 patients (ALL 16/25, AML 25/32, CLL 30/36, CML 10/21). Deletions were most often seen in ALL at 11q23 and 19p13; in AML at 8q22 and 11q23; in CLL at 13q14.3, 11q13, and 11q23; and in CML at 3q26. Only six deletions were reported in 74 karyotypes analyzed, whereas in these same cases, 91 LOH events were detected by microsatellites. Of 26 leukemias with a normal karyotype, 16 nevertheless showed at least one LOH by microsatellite analysis. Replication errors were found in 10 of 114 patients (8.8%). Thus, microsatellite instability is rare in leukemia in contrast to many solid tumors. Our findings suggest that in adult leukemia, LOH may be an important genetic event in addition to typical chromosomal translocations. LOH may point to the existence of tumor suppressor genes involved in leukemogenesis to a degree that has hitherto been underestimated.
Keywords
Adult, Chromosome Aberrations, Clone Cells, DNA Mutational Analysis, DNA Replication, DNA, Neoplasm, Genes, Tumor Suppressor, Heterozygote, Humans, Leukemia, Microsatellite Repeats, Neoplastic Stem Cells, Sequence Deletion
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Web of science
Create date
22/05/2009 10:22
Last modification date
20/08/2019 15:27
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