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

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Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia. / Gunnarsson, Rebeqa; Mansouri, Larry; Isaksson, Anders; Goransson, Hanna; Cahill, Nicola; Jansson, Mattias; Rasmussen, Markus; Lundin, Jeanette; Norin, Stefan; Buhl, Anne Mette; Smedby, Karin Ekstrom; Hjalgrim, Henrik; Karlsson, Karin; Jurlander, Jesper; Geisler, Christian; Juliusson, Gunnar; Rosenquist, Richard.

I: Haematologica, Vol. 96, Nr. 8, 2011, s. 1161-1169.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Gunnarsson, R, Mansouri, L, Isaksson, A, Goransson, H, Cahill, N, Jansson, M, Rasmussen, M, Lundin, J, Norin, S, Buhl, AM, Smedby, KE, Hjalgrim, H, Karlsson, K, Jurlander, J, Geisler, C, Juliusson, G & Rosenquist, R 2011, 'Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia', Haematologica, vol. 96, nr. 8, s. 1161-1169. https://doi.org/10.3324/haematol.2010.039768

APA

Gunnarsson, R., Mansouri, L., Isaksson, A., Goransson, H., Cahill, N., Jansson, M., ... Rosenquist, R. (2011). Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia. Haematologica, 96(8), 1161-1169. https://doi.org/10.3324/haematol.2010.039768

CBE

Gunnarsson R, Mansouri L, Isaksson A, Goransson H, Cahill N, Jansson M, Rasmussen M, Lundin J, Norin S, Buhl AM, Smedby KE, Hjalgrim H, Karlsson K, Jurlander J, Geisler C, Juliusson G, Rosenquist R. 2011. Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia. Haematologica. 96(8):1161-1169. https://doi.org/10.3324/haematol.2010.039768

MLA

Vancouver

Author

Gunnarsson, Rebeqa ; Mansouri, Larry ; Isaksson, Anders ; Goransson, Hanna ; Cahill, Nicola ; Jansson, Mattias ; Rasmussen, Markus ; Lundin, Jeanette ; Norin, Stefan ; Buhl, Anne Mette ; Smedby, Karin Ekstrom ; Hjalgrim, Henrik ; Karlsson, Karin ; Jurlander, Jesper ; Geisler, Christian ; Juliusson, Gunnar ; Rosenquist, Richard. / Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia. I: Haematologica. 2011 ; Vol. 96, Nr. 8. s. 1161-1169.

RIS

TY - JOUR

T1 - Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia

AU - Gunnarsson, Rebeqa

AU - Mansouri, Larry

AU - Isaksson, Anders

AU - Goransson, Hanna

AU - Cahill, Nicola

AU - Jansson, Mattias

AU - Rasmussen, Markus

AU - Lundin, Jeanette

AU - Norin, Stefan

AU - Buhl, Anne Mette

AU - Smedby, Karin Ekstrom

AU - Hjalgrim, Henrik

AU - Karlsson, Karin

AU - Jurlander, Jesper

AU - Geisler, Christian

AU - Juliusson, Gunnar

AU - Rosenquist, Richard

PY - 2011

Y1 - 2011

N2 - Background 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. Design and Methods 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. Results 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 IGHV, and in 4/25 (16%) IGHV-mutated and treated patients. In contrast, untreated patients with mutated IGHV (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 IGHV. 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.

AB - Background 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. Design and Methods 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. Results 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 IGHV, and in 4/25 (16%) IGHV-mutated and treated patients. In contrast, untreated patients with mutated IGHV (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 IGHV. 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.

KW - chronic lymphocytic leukemia

KW - SNP-array

KW - genomic aberrations

KW - CNN-LOH

KW - clonal evolution

U2 - 10.3324/haematol.2010.039768

DO - 10.3324/haematol.2010.039768

M3 - Article

VL - 96

SP - 1161

EP - 1169

JO - Haematologica-The Hematology Journal

T2 - Haematologica-The Hematology Journal

JF - Haematologica-The Hematology Journal

SN - 1592-8721

IS - 8

ER -