title: A high-resolution allelotype of B-cell chronic lymphocytic leukemia (B-CLL).
abstract: 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.
authors.affiliation: Department of Clinical Research and Medical Oncology/Hematology, Inselspital (University Hospital), Bern, Switzerland.
authors.forename: Urban
authors.initials: U
authors.lastname: Novak
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Oppliger Leibundgut
authors.forename: Jörg
authors.initials: J
authors.lastname: Hager
authors.forename: Dominique
authors.initials: D
authors.lastname: Mühlematter
authors.forename: Martine
authors.initials: M
authors.lastname: Jotterand
authors.forename: Celine
authors.initials: C
authors.lastname: Besse
authors.forename: Nicolas
authors.initials: N
authors.lastname: Leupin
authors.forename: Daniel
authors.initials: D
authors.lastname: Ratschiller
authors.forename: Jeanette
authors.initials: J
authors.lastname: Papp
authors.forename: Gina
authors.initials: G
authors.lastname: Kearsey
authors.forename: Stefan
authors.initials: S
authors.lastname: Aebi
authors.forename: Hans
authors.initials: H
authors.lastname: Graber
authors.forename: Rolf
authors.initials: R
authors.lastname: Jaggi
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lüthi
authors.forename: Sandrine
authors.initials: S
authors.lastname: Meyer-Monard
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Andreas
authors.initials: A
authors.lastname: Tobler
authors.forename: Martin F
authors.initials: MF
authors.lastname: Fey
mesh_terms: D000483:Alleles; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D006801:Humans; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction