Array-based genomic screening at diagnosis and follow-up in chronic lymphocytic leukemia

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BlankArray-based genomic screening at diagnosis and follow-up in chronic

lymphocytic leukemia.

R Gunnarsson, L Mansouri, A Isaksson, H Goransson, N Cahill, M Jansson, M

Rasmussen, J Lundin, S Norin, AM Buhl, K Ekstrom Smedby, H Hjalgrim, K Karlsson,

J Jurlander, C Geisler, G Juliusson, and R Rosenquist

Haematologica, May 5, 2011;

Sweden;

Background. High-resolution genomic microarrays provides simultaneous detection

of copy-number aberrations such as the known recurrent aberrations in chronic

lymphocytic leukemia (del(11q), del(13q), del(17p) and trisomy 12), and

copy-number neutral loss of heterozygosity. Moreover, comparison of genomic

profiles from sequential patient samples allows detection of clonal evolution.

Design and Methods. We screened 369 newly diagnosed chronic lymphocytic leukemia

patient samples from a population-based cohort using 250K single nucleotide

polymorphism-arrays. Clonal evolution was evaluated in 59 follow-up samples

obtained after 5-9 years. Results. At diagnosis, copy-number aberrations were

identified in 90% of patients and 70% carried the known recurrent alterations,

including del(13q) (55%), trisomy 12 (10.5%), del(11q) (10%), and del(17p) (4%).

Additional recurrent aberrations were detected on chromosome 2 (1.9%), 4 (1.4%),

8 (1.6%) and 14 (1.6%). Thirteen patients (3.5%) displayed recurrent copy-number

neutral loss of heterozygosity on 13q, whereof 11 concurred with a homozygous

del(13q). Genomic complexity and large 13q deletions correlated with inferior

outcome, where the former was linked to poor-prognostic aberrations. In the

follow-up study, clonal evolution developed in 8/24 (33%) IGHV unmutated

patients, and in 4/25 (16%) IGHV mutated and treated patients. In contrast,

untreated IGHV mutated patients (n=10) did not acquire additional aberrations.

The most common secondary event, del(13q), was detected in 6/12 (50%) of all

patients with acquired alterations. Interestingly, aberrations on e.g.

chromosome 6q, 8p, 9p and 10q developed exclusively in IGHV unmutated patients.

Conclusions. Whole-genome screening revealed a high frequency of genomic

aberrations in newly diagnosed chronic lymphocytic leukemia. Clonal evolution

was associated with other markers of aggressive disease and commonly included

the known recurrent aberrations.

PMID: 21546498