title: More extensive genetic alterations in unmutated than in hypermutated cases of chronic lymphocytic leukemia.
abstract: B-cell chronic lymphocytic leukemia (CLL) is not a uniform disease entity; approximately half of the CLL cases have undergone immunoglobulin V(H) gene hypermutation, whereas the other half display unmutated V(H) genes. We investigated genome changes in 12 hypermutated cases (M-CLL) and 22 unmutated cases (UM-CLL) by use of comparative genomic hybridization, G-banding, and multicolor fluorescence in situ hybridization (m-FISH) after optimal mitogen stimulation and FISH analysis of typical CLL aberrations: 11q deletion, 13q deletion, and trisomy 12. Very high frequencies of aberrations were found in both groups: 82% in UM-CLL and 83% in M-CLL. Deletions of 11q and 13q were equally distributed in M-CLL and UM-CLL. However, larger aberrations detectable by CGH, trisomy 12, and complex aberrations were less frequent in M-CLL than in UM-CLL. These observations led to a hypothesis that unmutated and mutated CLL have different biological Backgrounds, given that large and/or complex chromosomal aberrations and hypermutation of the CLL progenitor cells tend to be mutually exclusive.
authors.affiliation: Laboratory of Cancer Genetics, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Ritva
authors.initials: R
authors.lastname: Karhu
authors.forename: Gerard
authors.initials: G
authors.lastname: Tobin
authors.forename: Ulf
authors.initials: U
authors.lastname: Thunberg
authors.forename: Leena
authors.initials: L
authors.lastname: Vilpo
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
authors.forename: Juhani
authors.initials: J
authors.lastname: Vilpo
mesh_terms: D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region