Germline allele-specific expression of DAPK1 in chronic lymphocytic leukemia.
Germline allele-specific expression of DAPK1 in chronic lymphocytic leukemia.
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DOI：
10.1371/journal.pone.0055261
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Plass C
中科院分区：
文献类型：
--
作者：
Wei QX;Claus R;Hielscher T;Mertens D;Raval A;Oakes CC;Tanner SM;de la Chapelle A;Byrd JC;Stilgenbauer S;Plass C
我们之前报道了一种罕见的种系变异（c.1-6531），它导致死亡相关蛋白激酶1 （DAPK1）的等位基因特异性表达（ASE）和慢性淋巴细胞白血病（CLL）的易感性。我们研究了一组缺乏这种突变的CLL患者的DAPK1 ASE的存在。我们开发了一种新的策略，将单核苷酸引物延伸（SNuPE）与MALDI-TOF质谱相结合，并在120名CLL患者中检测出17名（14.2%）的种系DAPK1 ASE，这些患者在诊断时呈年轻化趋势。63例健康对照无ASE。CLL ASE患者的生殖细胞显示启动子区域DNA甲基化水平升高，然而，在DAPK1 5 ‘上游调控区、不同外显子内或3 ’ -UTR内均未发现遗传或进一步的表观遗传畸变。我们发现b淋巴细胞恶性肿瘤相关细胞系模型中存在等位基因失衡，并发现DAPK1等位基因特异性甲基化与ASE相关。我们的数据表明，DAPK1基因位点的ASE是一种复发性事件，由表观遗传机制介导，可能易患CLL。
We previously reported a rare germline variant (c.1-6531) that resulted in allele–specific expression (ASE) of death-associated protein kinase 1 (DAPK1) and predisposition to chronic lymphocytic leukemia (CLL). We investigated a cohort of CLL patients lacking this mutation for the presence of ASE of DAPK1. We developed a novel strategy that combines single-nucleotide primer extension (SNuPE) with MALDI-TOF mass spectrometry, and detected germline DAPK1 ASE in 17 out of 120 (14.2%) CLL patients associated with a trend towards younger age at diagnosis. ASE was absent in 63 healthy controls. Germline cells of CLL patients with ASE showed increased levels of DNA methylation in the promoter region, however, neither genetic nor further epigenetic aberrations could be identified in the DAPK1 5′ upstream regulatory region, within distinct exons or in the 3′-UTR. We identified B-lymphoid malignancy related cell line models harboring allelic imbalance and found that allele-specific methylation in DAPK1 is associated with ASE. Our data indicate that ASE at the DAPK1 gene locus is a recurrent event, mediated by epigenetic mechanisms and potentially predisposing to CLL.
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影响因子：
7
作者：
Lo, HS;Wang, ZN;Lee, MP
通讯作者：
Lee, MP
影响因子：
11.2
作者：
Guda, Kishore;Natale, Leanna;Markowitz, Sanford D.
通讯作者：
Markowitz, Sanford D.
影响因子：
10.6
作者：
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通讯作者：
Li, Ming D.
DOI：
10.1196/annals.1345.009
发表时间：
2005-01-01
期刊：
COOLEY'S ANEMIA EIGHTH SYMPOSIUM
影响因子：
--
作者：
Martin, DIK;Ward, R;Suter, CM
通讯作者：
Suter, CM
影响因子：
3.5
作者：
Pinheiro, Hugo;Bordeira-Carrico, Renata;Oliveira, Carla
通讯作者：
Oliveira, Carla