Molecular allelokaryotyping of early-stage, untreated chronic lymphocytic leukemia.
BACKGROUND
To the authors' knowledge, genetic abnormalities in early-stage chronic lymphocytic leukemia (CLL) have not been examined fully. Single nucleotide polymorphism (SNP) genomic array (SNP-chip) is a new tool that can detect copy number changes and uniparental disomy (UPD) over the entire genome with very high resolution.


METHODS
The authors performed SNP-chip analysis on 56 samples from patients with early-stage, untreated CLL. To validate the SNP-chip data, fluorescence in situ hybridization (FISH) analysis was performed at selected sites. Expression levels of ZAP-70 and the mutational status of immunoglobulin heavy-chain gene also were examined.


RESULTS
SNP-chip analysis easily detected nearly all changes that were identified by FISH, including trisomy 12, deletion of TP53 (17p13), deletion of ATM (11q22), and deletion of 13q14. Only 10 of 56 CLL samples (18%) had no genomic abnormalities. Excluding the 4 common abnormalities mentioned above, 25 CLL samples (45%) had a total of 45 copy number changes detected by SNP-chip analysis. Four samples had 6q deletion at 6q21 that involved the AIM1 gene. UPD was detected in 4 samples; 2 samples involved whole chromosome 13 resulting in homozygous deletion of micro-RNA-15a (miR-15a)/miR-16-1. CLL samples with deletion of 13q14 and trisomy 12 were mutually exclusive.


CONCLUSIONS
Genetic abnormalities, including whole chromosome 13 UPD, are very common events in early-stage CLL. SNP-chip analysis can detect small genetic abnormalities in CLL and may be able to support or even supplant FISH and cytogenetics.
Lehmann
Sören
S
Department of Hematology/Oncology, Cedars-Sinai Medical Center, University of California at Los Angeles School of Medicine, Los Angeles, California 90048, USA.
Ogawa
Seishi
S
Raynaud
Sophie D
SD
Sanada
Masashi
M
Nannya
Yasuhito
Y
Ticchioni
Michel
M
Bastard
Christian
C
Kawamata
Norihiko
N
Koeffler
H Phillip
HP
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002869:Chromosome Aberrations; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D015331:Cohort Studies; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D015894:Genome, Human; D006801:Humans; D007143:Immunoglobulin Heavy Chains; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics
D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains; D012333:RNA, Messenger; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human