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More extensive genetic alterations in unmutated than in hypermutated cases of chronic lymphocytic leukemia
Author(s) -
Karhu Ritva,
Tobin Gerard,
Thunberg Ulf,
Vilpo Leena,
Sundström Christer,
Knuutila Sakari,
Rosenquist Richard,
Vilpo Juhani
Publication year - 2003
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.10227
Subject(s) - chronic lymphocytic leukemia , somatic hypermutation , biology , trisomy , fluorescence in situ hybridization , comparative genomic hybridization , genetics , microbiology and biotechnology , cancer research , leukemia , gene , antibody , genome , chromosome , b cell
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. © 2003 Wiley‐Liss, Inc.