More extensive genetic alterations in unmutated than in hypermutated cases of chronic lymphocytic leukemia.
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.
Karhu
Ritva
R
Laboratory of Cancer Genetics, University of Tampere and Tampere University Hospital, Tampere, Finland.
Tobin
Gerard
G
Thunberg
Ulf
U
Vilpo
Leena
L
Sundström
Christer
C
Knuutila
Sakari
S
Rosenquist
Richard
R
Vilpo
Juhani
J
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
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region