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Detection of chromothripsis-like patterns with a custom array platform for
chronic lymphocytic leukemia
#MMPMID26305789
Salaverria I
; Martín-Garcia D
; López C
; Clot G
; García-Aragonés M
; Navarro A
; Delgado J
; Baumann T
; Pinyol M
; Martin-Guerrero I
; Carrió A
; Costa D
; Queirós AC
; Jayne S
; Aymerich M
; Villamor N
; Colomer D
; González M
; López-Guillermo A
; Campo E
; Dyer MJ
; Siebert R
; Armengol L
; Beà S
Genes Chromosomes Cancer
2015[Nov]; 54
(11
): 668-80
PMID26305789
show ga
Chronic lymphocytic leukemia (CLL) is a common disease with highly variable
clinical course. Several recurrent chromosomal alterations are associated with
prognosis and may guide risk-adapted therapy. We have developed a targeted
genome-wide array to provide a robust tool for ascertaining abnormalities in CLL
and to overcome limitations of the 4-marker fluorescence in situ hybridization
(FISH). DNA from 180 CLL patients were hybridized to the qChip®Hemo array with a
high density of probes covering commonly altered loci in CLL (11q22-q23, 13q14,
and 17p13), nine focal regions (2p15-p16.1, 2p24.3, 2q13, 2q36.3-q37.1, 3p21.31,
8q24.21, 9p21.3, 10q24.32, and 18q21.32-q21.33) and two larger regions
(6q14.1-q22.31 and 7q31.33-q33). Overall, 86% of the cases presented copy number
alterations (CNA) by array. There was a high concordance of array findings with
FISH (84% sensitivity, 100% specificity); all discrepancies corresponded to
subclonal alterations detected only by FISH. A chromothripsis-like pattern was
detected in eight cases. Three showed concomitant shattered 5p with gain of TERT
along with isochromosome 17q. Presence of 11q loss was associated with shorter
time to first treatment (P?=?0.003), whereas 17p loss, increased genomic
complexity, and chromothripsis were associated with shorter overall survival
(P?0.001, P?=?0.001, and P?=?0.02, respectively). In conclusion, we have
validated a targeted array for the diagnosis of CLL that accurately detects, in a
single experiment, all relevant CNAs, genomic complexity, chromothripsis, copy
number neutral loss of heterozygosity, and CNAs not covered by the FISH panel.
This test may be used as a practical tool to stratify CLL patients for routine
diagnostics or clinical trials.