Journal article
Array Comparative Genomic Hybridization Analysis Identifies Recurrent Gain of Chromosome 2p25.3 Involving the ACP1 and MYCN Genes in Chronic Lymphocytic Leukemia
Clinical lymphoma, myeloma and leukemia, Vol.11(Suppl 1), pp.S17-S24
06/2011
DOI: 10.1016/j.clml.2011.03.031
PMCID: PMC4845643
PMID: 22035742
Abstract
Chromosomal aberrations are independent prognostic markers in chronic lymphocytic leukemia (CLL). Recent studies using genomic arrays have shown recurrent gains of the short arm of chromosome 2 (2p) in a subset of CLL. We evaluated 178 CLL cases for 2p gains using custom-designed oligonucleotide array-based comparative genomic hybridization (aCGH). A high frequency of 2p gains was observed in 53 of 178 (30%) cases, which ranged from a small 29-kb region to large segments involving the entire short arm. Besides several common chromosomal aberrations associated with 2p gain, we demonstrated a novel observation that gain of the telomeric region 2p25.3 harboring the
ACP1
gene is common in CLL (25%, 44 of 178 cases). The
ACP1
gene has been previously shown to regulate T-cell receptor signaling through
ZAP-70
, and both genes are unfavorable clinical markers for CLL. Quantitative polymerase chain reaction (qPCR) confirmed the presence of 3–6 copies of
ACP1
in 35 of 40 (88%) of these cases. Interestingly, none of the aCGH diploid CLL cases showed gain of
ACP1
. Assessment of 73 healthy individuals by qPCR revealed
ACP1
copy number gain in only two cases (2.7%). Gain of 2p25.3 was associated with ZAP-70 expression (
P
< .002) and unmutated immunoglobulin heavy chain variable (
IGHV
) gene mutation (
P
<.0001). A high frequency of
MYCN
co-amplication with
ACP1
was observed (14 of 40 cases, 35%). The frequent 2p25.3 gain involving the
ACP1
and
MYCN
genes may help define the critical region of 2p that contributes to pathogenesis of CLL together with other chromosomal abnormalities.
Details
- Title: Subtitle
- Array Comparative Genomic Hybridization Analysis Identifies Recurrent Gain of Chromosome 2p25.3 Involving the ACP1 and MYCN Genes in Chronic Lymphocytic Leukemia
- Creators
- Deqin Ma - Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TXZhao Chen - Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TXKeyur P Patel - Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TXBal M Mishra - Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TXHui Yao - Department of Bioinformatics, University of Texas MD Anderson Cancer Center, Houston, TXLynne V Abruzzo - Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TXL. Jeffrey Medeiros - Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TXWilliam Wierda - Department of Leukemia, the University of Texas M.D. Anderson Cancer Center, Houston, TXMichael Keating - Department of Leukemia, the University of Texas M.D. Anderson Cancer Center, Houston, TXRachel Sargent - Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TXRajyalakshmi Luthra - Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX
- Resource Type
- Journal article
- Publication Details
- Clinical lymphoma, myeloma and leukemia, Vol.11(Suppl 1), pp.S17-S24
- DOI
- 10.1016/j.clml.2011.03.031
- PMID
- 22035742
- PMCID
- PMC4845643
- NLM abbreviation
- Clin Lymphoma Myeloma Leuk
- ISSN
- 2152-2650
- eISSN
- 2152-2669
- Language
- English
- Date published
- 06/2011
- Academic Unit
- Pathology
- Record Identifier
- 9984047889002771
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