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: Ritva Karhu, Gerard Tobin, Ulf Thunberg, Leena Vilpo, Christer Sundström, Sakari Knuutila, Richard Rosenquist, Juhani Vilpo
• Journal: Genes, chromosomes & cancer (Genes Chromosomes Cancer) Vol. 37 Issue 4 Pg. 417-20 (Aug 2003) ISSN: 1045-2257 [Print] United States
• PMID: 12800154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Immunoglobulin Heavy Chains
• Immunoglobulin Variable Region

Topics

• Chromosome Aberrations
• Chromosome Deletion
• Female
• Gene Amplification (genetics)
• Humans
• Immunoglobulin Heavy Chains (genetics)
• Immunoglobulin Variable Region (genetics)
• Karyotyping
• Leukemia, Lymphocytic, Chronic, B-Cell (genetics)
• Male