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

Gunnarsson, Rebeqa LU ; Mansouri, Larry; Isaksson, Anders; Goransson, Hanna; Cahill, Nicola; Jansson, Mattias; Rasmussen, Markus; Lundin, Jeanette; Norin, Stefan and Buhl, Anne Mette, et al. (2011) In Haematologica 96(8). p.1161-1169
Abstract
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... (More)
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. (Less)
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keywords
chronic lymphocytic leukemia, SNP-array, genomic aberrations, CNN-LOH, clonal evolution
in
Haematologica
volume
96
issue
8
pages
1161 - 1169
publisher
Ferrata Storti Foundation
external identifiers
  • wos:000294722700014
  • scopus:79961059215
ISSN
1592-8721
DOI
10.3324/haematol.2010.039768
language
English
LU publication?
yes
id
1a286fd8-79c4-47da-8491-8e58a27468ba (old id 2186964)
date added to LUP
2011-11-01 07:52:55
date last changed
2017-10-22 04:16:59
@article{1a286fd8-79c4-47da-8491-8e58a27468ba,
  abstract     = {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.},
  author       = {Gunnarsson, Rebeqa and Mansouri, Larry and Isaksson, Anders and Goransson, Hanna and Cahill, Nicola and Jansson, Mattias and Rasmussen, Markus and Lundin, Jeanette and Norin, Stefan and Buhl, Anne Mette and Smedby, Karin Ekstrom and Hjalgrim, Henrik and Karlsson, Karin and Jurlander, Jesper and Geisler, Christian and Juliusson, Gunnar and Rosenquist, Richard},
  issn         = {1592-8721},
  keyword      = {chronic lymphocytic leukemia,SNP-array,genomic aberrations,CNN-LOH,clonal evolution},
  language     = {eng},
  number       = {8},
  pages        = {1161--1169},
  publisher    = {Ferrata Storti Foundation},
  series       = {Haematologica},
  title        = {Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia},
  url          = {http://dx.doi.org/10.3324/haematol.2010.039768},
  volume       = {96},
  year         = {2011},
}