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A high-resolution allelotype of B-cell chronic lymphocytic leukemia (B-CLL)

  • Novak, Urban From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Oppliger Leibundgut, Elisabeth From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Hager, Jörg From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Mühlematter, Dominique From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Jotterand, Martine From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Besse, Celine From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Leupin, Nicolas From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Ratschiller, Daniel From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Papp, Jeanette From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Kearsey, Gina From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Aebi, Stefan From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Graber, Hans From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Jaggi, Rolf From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Lüthi, Jean-Marc From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Meyer-Monard, Sandrine From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Lathrop, Mark From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Tobler, Andreas From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
  • Fey, Martin F. From the Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland; the Centre National de Génotypage, Evry, France; the Division of Medical Genetics, University Hospital, Lausanne, Switzerland; the Department of Human Genetics, University of California, Los Angeles; the Department of Medicine, Regionalspital, Thun, Switzerland; and the Department of Hematology/Central Laboratories, University Hospital, Basel, Switzerland.
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  • Blood. - American Society of Hematology. - 2002, vol. 100, no. 5, p. 1787-1794
Immunology
Cell Biology
Biochemistry
Hematology
English The most frequent chromosomal aberrations in B-cell chronic lymphocytic leukemia (B-CLL) are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance. Conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) are used for their detection, but cytogenetic analysis is hampered by the low mitotic index of B-CLL cells, and FISH depends on accurate information about candidate regions. We used a set of 400 highly informative microsatellite markers covering all chromosomal arms (allelotyping) and automated polymerase chain reaction (PCR) protocols to screen 46 patients with typical B-CLL for chromosomal aberrations. For validation, we compared data with our conventional karyotype results and fine mapping with conventional single-site PCR. All clonal cytogenetic abnormalities potentially detectable by our microsatellite PCR (eg, del13q14 and trisomy 12) were picked up. Allelotyping revealed additional complex aberrations in patients with both normal and abnormal B-CLL karyotypes. Aberrations detectable in the samples with our microsatellite panel were found on almost all chromosomal arms. We detected new aberrant loci in typical B-CLL, such as allelic losses on 1q, 9q, and 22q in up to 25% of our patients, and allelic imbalances mirroring chromosomal duplications, amplifications, or aneuploidies on 2q, 10p, and 22q in up to 27% of our patients. We conclude that allelotyping with our battery of informative microsatellites is suitable for molecular screening of B-CLL. The technique is well suited for analyses in clinical trials, it provides a comprehensive view of genetic alterations, and it may identify new loci with candidate genes relevant in the molecular biology of B-CLL.
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  • English
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https://sonar.ch/global/documents/61091
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