Array comparative genomic hybridization analysis identifies recurrent gain of chromosome 2p25.3 involving the ACP1 and MYCN genes in chronic lymphocytic leukemia.
Array comparative genomic hybridization analysis identifies recurrent gain of chromosome 2p25.3 involving the ACP1 and MYCN genes in chronic lymphocytic leukemia.
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阵列比较基因组杂交分析确定了涉及慢性淋巴细胞性白血病中ACP1和MYCN基因的2p25.3染色体的复发增益。
DOI：
10.1016/j.clml.2011.03.031
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Luthra R
中科院分区：
文献类型：
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作者：
Ma D;Chen Z;Patel KP;Mishra BM;Yao H;Abruzzo LV;Medeiros LJ;Wierda W;Keating M;Sargent R;Luthra R
染色体畸变是慢性淋巴细胞白血病（CLL）的独立预后标志物。最近使用基因组阵列的研究表明，CLL 子集中 2 号染色体短臂 (2p) 反复出现。我们使用定制设计的基于寡核苷酸阵列的比较基因组杂交 (aCGH) 评估了 178 个 CLL 病例的 2p 增益。在 178 例中的 53 例 (30%) 中观察到高频率的 2p 增益，范围从 29 kb 的小区域到涉及整个短臂的大片段。除了与 2p 增益相关的几种常见染色体畸变之外，我们还证明了一项新的观察结果，即包含 ACP1 基因的端粒区域 2p25.3 的增益在 CLL 中很常见（25%，178 例中的 44 例）。 ACP1 基因之前已被证明可以通过 ZAP-70 调节 T 细胞受体信号传导，这两个基因都是 CLL 的不利临床标志物。定量聚合酶链反应 (qPCR) 证实，40 例病例中有 35 例 (88%) 存在 3-6 个 ACP1 拷贝。有趣的是，aCGH 二倍体 CLL 病例均未表现出 ACP1 的增加。通过 qPCR 对 73 名健康个体进行的评估显示，只有两例 (2.7%) 的 ACP1 拷贝数增加。 2p25.3 的增加与 ZAP-70 表达 (P < .002) 和未突变的免疫球蛋白重链可变 (IGHV) 基因突变 (P < .0001) 相关。观察到 MYCN 与 ACP1 合并并发症的频率较高（40 例中有 14 例，35%）。涉及 ACP1 和 MYCN 基因的 2p25.3 频繁增益可能有助于确定 2p 的关键区域，该区域导致 CLL 以及其他染色体异常的发病机制。
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.