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Detection of chromothripsis‐like patterns with a custom array platform for chronic lymphocytic leukemia
Author(s) -
Salaverria Itziar,
MartínGarcia David,
López Cristina,
Clot Guillem,
GarcíaAragonés Manel,
Navarro Alba,
Delgado Julio,
Baumann Tycho,
Pinyol Magda,
MartinGuerrero Idoia,
Carrió Ana,
Costa Dolors,
Queirós Ana C.,
Jayne Sandrine,
Aymerich Marta,
Villamor Neus,
Colomer Dolors,
González Marcos,
LópezGuillermo Armando,
Campo Elías,
Dyer Martin J. S.,
Siebert Reiner,
Armengol Lluís,
Beà Sílvia
Publication year - 2015
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22277
Subject(s) - chronic lymphocytic leukemia , chromothripsis , computational biology , computer science , leukemia , cancer research , medicine , biology , genetics , dna , genome instability , dna damage
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. © 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.