@article{Rebeqa Gunnarsson_Larry Mansouri_Anders Isaksson_Hanna Göransson_Nicola Cahill_Mattias Jansson_Markus Rasmussen_Jeanette Lundin_Stefan Norin_Anne Mette Buhl_Karin Ekström Smedby_Henrik Hjalgrim_Karin Karlsson_Jesper Jurlander_Christian Geisler_Gunnar Juliusson_Richard Rosenquist_2011, place={Pavia, Italy}, title={Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia}, volume={96}, url={https://haematologica.org/article/view/6043}, DOI={10.3324/haematol.2010.039768}, abstractNote={<strong>Background</strong> High-resolution genomic microarrays enable 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 patients’ samples allows detection of clonal evolution.<strong>Design and Methods</strong> We screened samples from 369 patients with newly diagnosed chronic lymphocytic leukemia 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.<strong>Results</strong> At diagnosis, copy-number aberrations were identified in 90% of patients; 70% carried known recurrent alterations, including del(13q) (55%), trisomy 12 (10.5%), del(11q) (10%), and del(17p) (4%). Additional recurrent aberrations were detected on chromosomes 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, of whom 11 had concurrent homozygous del(13q). Genomic complexity and large 13q deletions correlated with inferior outcome, while the former was linked to poor-prognostic aberrations. In the follow-up study, clonal evolution developed in 8/24 (33%) patients with unmutated <em>IGHV</em>, and in 4/25 (16%) <em>IGHV</em>-mutated and treated patients. In contrast, untreated patients with mutated <em>IGHV</em> (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, for example, chromosome 6q, 8p, 9p and 10q developed exclusively in patients with unmutated <em>IGHV</em>.<strong>Conclusions</strong&gt; 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.}, number={8}, journal={Haematologica}, author={Rebeqa Gunnarsson and Larry Mansouri and Anders Isaksson and Hanna Göransson and Nicola Cahill and Mattias Jansson and Markus Rasmussen and Jeanette Lundin and Stefan Norin and Anne Mette Buhl and Karin Ekström Smedby and Henrik Hjalgrim and Karin Karlsson and Jesper Jurlander and Christian Geisler and Gunnar Juliusson and Richard Rosenquist}, year={2011}, month={Aug.}, pages={1161-1169} }