PMID- 26305789
OWN - NLM
STAT- MEDLINE
DCOM- 20160613
LR  - 20220129
IS  - 1098-2264 (Electronic)
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 54
IP  - 11
DP  - 2015 Nov
TI  - Detection of chromothripsis-like patterns with a custom array platform for 
      chronic lymphocytic leukemia.
PG  - 668-80
LID - 10.1002/gcc.22277 [doi]
AB  - 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(R)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.
CI  - (c) 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, 
      Inc.
FAU - Salaverria, Itziar
AU  - Salaverria I
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
FAU - Martin-Garcia, David
AU  - Martin-Garcia D
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
FAU - Lopez, Cristina
AU  - Lopez C
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
AD  - Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus 
      Kiel/Christian-Albrechts University, Kiel, Germany.
FAU - Clot, Guillem
AU  - Clot G
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
FAU - Garcia-Aragones, Manel
AU  - Garcia-Aragones M
AD  - R&D, Department, Quantitative Genomic Medicine Laboratories (qGenomics), 
      Barcelona, Spain.
FAU - Navarro, Alba
AU  - Navarro A
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
FAU - Delgado, Julio
AU  - Delgado J
AD  - Department of Hematology, Hospital Clinic, IDIBAPS, Barcelona, Spain.
FAU - Baumann, Tycho
AU  - Baumann T
AD  - Department of Hematology, Hospital Clinic, IDIBAPS, Barcelona, Spain.
FAU - Pinyol, Magda
AU  - Pinyol M
AD  - Genomics Unit, Institut d'Investigacions Biomediques August Pi i Sunyer 
      (IDIBAPS), Barcelona, Spain.
FAU - Martin-Guerrero, Idoia
AU  - Martin-Guerrero I
AD  - Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus 
      Kiel/Christian-Albrechts University, Kiel, Germany.
AD  - Department of Genetics, Physical Anthropology and Animal Physiology, University 
      of the Basque Country, Leioa, Spain.
FAU - Carrio, Ana
AU  - Carrio A
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
FAU - Costa, Dolors
AU  - Costa D
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
FAU - Queiros, Ana C
AU  - Queiros AC
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
FAU - Jayne, Sandrine
AU  - Jayne S
AD  - Ernest and Helen Scott Haematological Research Institute, Department of 
      Biochemistry, University of Leicester, Leicester, UK.
FAU - Aymerich, Marta
AU  - Aymerich M
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
FAU - Villamor, Neus
AU  - Villamor N
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
FAU - Colomer, Dolors
AU  - Colomer D
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
FAU - Gonzalez, Marcos
AU  - Gonzalez M
AD  - Department of Hematology, Hospital Clinico-IBSAL, Cancer Institute of 
      Salamanca-IBMCC (USAL-CSIC), Salamanca, Spain.
FAU - Lopez-Guillermo, Armando
AU  - Lopez-Guillermo A
AD  - Department of Hematology, Hospital Clinic, IDIBAPS, Barcelona, Spain.
FAU - Campo, Elias
AU  - Campo E
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
FAU - Dyer, Martin J S
AU  - Dyer MJ
AD  - Ernest and Helen Scott Haematological Research Institute, Department of 
      Biochemistry, University of Leicester, Leicester, UK.
FAU - Siebert, Reiner
AU  - Siebert R
AD  - Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus 
      Kiel/Christian-Albrechts University, Kiel, Germany.
FAU - Armengol, Lluis
AU  - Armengol L
AD  - R&D, Department, Quantitative Genomic Medicine Laboratories (qGenomics), 
      Barcelona, Spain.
FAU - Bea, Silvia
AU  - Bea S
AD  - Hematopathology Unit, Hospital Clinic Institut d'Investigacions Biomediques 
      August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
LA  - eng
GR  - 12-0142/AICR_/Worldwide Cancer Research/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20150825
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Chromosome Aberrations
MH  - Female
MH  - Gene Dosage
MH  - Genome, Human
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis/*genetics
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Oligonucleotide Array Sequence Analysis/methods
PMC - PMC4832286
EDAT- 2015/08/26 06:00
MHDA- 2016/06/14 06:00
PMCR- 2016/04/15
CRDT- 2015/08/26 06:00
PHST- 2015/04/13 00:00 [received]
PHST- 2015/06/04 00:00 [revised]
PHST- 2015/06/04 00:00 [accepted]
PHST- 2015/08/26 06:00 [entrez]
PHST- 2015/08/26 06:00 [pubmed]
PHST- 2016/06/14 06:00 [medline]
PHST- 2016/04/15 00:00 [pmc-release]
AID - GCC22277 [pii]
AID - 10.1002/gcc.22277 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2015 Nov;54(11):668-80. doi: 10.1002/gcc.22277. Epub 
      2015 Aug 25.