Genome Profiling Reveals Novel Genetic Subtypes

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[2090] Genomic Profiling of Chronic Lymphocytic Leukemia Identifies

Novel Genetic Subtypes. Session Type: Poster Session, Board #268-II

Sami N. Malek, A. Kujawski, Harry P. Erba, Mark S. Kaminski,

Andrzej Jakubowiak, Dressel, M. Saddler, Kerby A.

Shedden, D. Ouillette Internal Medicine, Hematology/Oncology,

University of Michigan, Ann Arbor, MI, USA; Department of Statistics,

University of Michigan, Ann Arbor, MI, USA

CLL is the most common leukemia in the Western world and displays

considerable clinical heterogeneity. Genetic approaches to elucidate

defects in CLL genomes have resulted in the identification of

recurrent chromosomal abnormalities with prognostic importance.

A genome-wide high-density unbiased view of chromosomal copy number

changes or loss of heterozygosity (LOH) may allow for further

refinements of genomics-based risk prognostication.

We have conducted a genomic profiling study using 50KSNP-

oligonucleotide arrays (Affymetrix) on FACS-sorted CD19+ cells and

paired buccal DNA from 120 patients with typical CLL (CD5+/CD23+) at

various stages of presentation enrolled in a clinical translational

protocol. We have found novel genetic subtypes, including novel

regions of recurrent LOH and chromosomal copy loss on chromosomes 3p,

14q and 18p at frequencies of 3-6%.

Fine mapping of the clinically important regions del(6q), del(11q),

del(13q14) and del(17p) suggests molecular heterogeneity of these

lesions.

Anatomic criteria suggest existence of multiple distinct subtypes of

del13q14. Furthermore, the clinically important del(17p) is

associated with almost uniform deletion of most of 17p, occasionally

displays copy-neutral LOH (undetectable by FISH) with p53 mutations

and occurs without p53 mutations in a subset of patients as

previously reported.

Finally, using a genome-wide composite genomic instability score of

copy gains and losses we found a subset of CLL cases (18%) with high

genomic instability values (greater than 2 lesions per genome). These

findings may have implications for CLL risk-adapted therapies.