PMID- 22285017
OWN - NLM
STAT- MEDLINE
DCOM- 20120326
LR  - 20120130
IS  - 2210-7762 (Print)
VI  - 204
IP  - 12
DP  - 2011 Dec
TI  - Clonal diversity analysis using SNP microarray: a new prognostic tool for chronic 
      lymphocytic leukemia.
PG  - 654-65
LID - 10.1016/j.cancergen.2011.10.012 [doi]
AB  - Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease. The 
      methods currently used for monitoring CLL and determining conditions for 
      treatment are limited in their ability to predict disease progression, patient 
      survival, and response to therapy. Although clonal diversity and the acquisition 
      of new chromosomal abnormalities during the disease course (clonal evolution) 
      have been associated with disease progression, their prognostic potential has 
      been underappreciated because cytogenetic and fluorescence in situ hybridization 
      (FISH) studies have a restricted ability to detect genomic abnormalities and 
      clonal evolution. We hypothesized that whole genome analysis using high 
      resolution single nucleotide polymorphism (SNP) microarrays would be useful to 
      detect diversity and infer clonal evolution to offer prognostic information. In 
      this study, we used the Infinium Omni1 BeadChip (Illumina, San Diego, CA) array 
      for the analysis of genetic variation and percent mosaicism in 25 non-selected 
      CLL patients to explore the prognostic value of the assessment of clonal 
      diversity in patients with CLL. We calculated the percentage of mosaicism for 
      each abnormality by applying a mathematical algorithm to the genotype frequency 
      data and by manual determination using the Simulated DNA Copy Number (SiDCoN) 
      tool, which was developed from a computer model of mosaicism. At least one 
      genetic abnormality was identified in each case, and the SNP data was 98% 
      concordant with FISH results. Clonal diversity, defined as the presence of two or 
      more genetic abnormalities with differing percentages of mosaicism, was observed 
      in 12 patients (48%), and the diversity correlated with the disease stage. Clonal 
      diversity was present in most cases of advanced disease (Rai stages III and IV) 
      or those with previous treatment, whereas 9 of 13 patients without detected 
      clonal diversity were asymptomatic or clinically stable. In conclusion, SNP 
      microarray studies with simultaneous evaluation of genomic alterations and mosaic 
      distribution of clones can be used to assess apparent clonal evolution via 
      analysis of clonal diversity. Since clonal evolution in CLL is strongly 
      correlated with disease progression, whole genome SNP microarray analysis 
      provides a new comprehensive and reliable prognostic tool for CLL patients.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Zhang, Linsheng
AU  - Zhang L
AD  - Department of Pathology and Laboratory Medicine, Medical University of South 
      Carolina, Charleston, USA.
FAU - Znoyko, Iya
AU  - Znoyko I
FAU - Costa, Luciano J
AU  - Costa LJ
FAU - Conlin, Laura K
AU  - Conlin LK
FAU - Daber, Robert D
AU  - Daber RD
FAU - Self, Sally E
AU  - Self SE
FAU - Wolff, Daynna J
AU  - Wolff DJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Genet
JT  - Cancer genetics
JID - 101539150
SB  - IM
MH  - Adult
MH  - Aged
MH  - Female
MH  - Genotype
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*diagnosis/genetics
MH  - Male
MH  - Middle Aged
MH  - Mosaicism
MH  - *Oligonucleotide Array Sequence Analysis
MH  - *Polymorphism, Single Nucleotide
MH  - Prognosis
EDAT- 2012/01/31 06:00
MHDA- 2012/03/27 06:00
CRDT- 2012/01/31 06:00
PHST- 2011/05/13 00:00 [received]
PHST- 2011/10/25 00:00 [revised]
PHST- 2011/10/28 00:00 [accepted]
PHST- 2012/01/31 06:00 [entrez]
PHST- 2012/01/31 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
AID - S2210-7762(11)00305-X [pii]
AID - 10.1016/j.cancergen.2011.10.012 [doi]
PST - ppublish
SO  - Cancer Genet. 2011 Dec;204(12):654-65. doi: 10.1016/j.cancergen.2011.10.012.