Identification of acquired mutations by whole-genome sequencing in GATA-2 deficiency evolving into myelodysplasia and acute leukemia.
Identification of acquired mutations by whole-genome sequencing in GATA-2 deficiency evolving into myelodysplasia and acute leukemia.
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DOI：
10.1007/s00277-014-2090-4
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发表时间：
2014-09
影响因子：
3.5
通讯作者：
Harigae, Hideo
中科院分区：
文献类型：
--
作者：
Fujiwara, Tohru;Fukuhara, Noriko;Funayama, Ryo;Nariai, Naoki;Kamata, Mayumi;Nagashima, Takeshi;Kojima, Kaname;Onishi, Yasushi;Sasahara, Yoji;Ishizawa, Kenichi;Nagasaki, Masao;Nakayama, Keiko;Harigae, Hideo
杂合加塔-2种系突变与称为加塔-2缺陷的重叠临床表现相关，其特征在于免疫缺陷和骨髓增生异常综合征（MDS）和急性髓性白血病（AML）的易感性。然而，患者之间存在相当大的临床异质性，免疫缺陷演变为MDS/AML的分子基础仍然未知。因此，我们对一个具有生殖系加塔-2杂合突变的患者进行了全基因组测序（c. 988 C > T; p.R330X），其具有提示免疫缺陷的病史并演变成MDS/AML。对免疫缺陷的白细胞、MDS的骨髓单核细胞和骨髓源性间充质干细胞的DNA样本进行分析。尽管我们没有鉴定出可能导致MDS演变的候选基因组缺失，但共鉴定出280种MDS特异性非同义单核苷酸变异。通过缩小与单核苷酸多态性数据库，功能错义数据库，和NCBI信息，我们最终确定了EZH 2，HECW 2和加塔-1，这可能有助于疾病的演变的三个候选突变。本文的在线版本（doi：10.1007/s 00277 -014-2090-4）包含补充材料，可供授权用户使用。
Heterozygous GATA-2 germline mutations are associated with overlapping clinical manifestations termed GATA-2 deficiency, characterized by immunodeficiency and predisposition to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, there is considerable clinical heterogeneity among patients, and the molecular basis for the evolution of immunodeficiency into MDS/AML remains unknown. Thus, we conducted whole-genome sequencing on a patient with a germline GATA-2 heterozygous mutation (c. 988 C > T; p. R330X), who had a history suggestive of immunodeficiency and evolved into MDS/AML. Analysis was conducted with DNA samples from leukocytes for immunodeficiency, bone marrow mononuclear cells for MDS and bone marrow-derived mesenchymal stem cells. Whereas we did not identify a candidate genomic deletion that may contribute to the evolution into MDS, a total of 280 MDS-specific nonsynonymous single nucleotide variants were identified. By narrowing down with the single nucleotide polymorphism database, the functional missense database, and NCBI information, we finally identified three candidate mutations for EZH2, HECW2 and GATA-1, which may contribute to the evolution of the disease. The online version of this article (doi:10.1007/s00277-014-2090-4) contains supplementary material, which is available to authorized users.
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影响因子：
16
作者：
Fujiwara T;O'Geen H;Keles S;Blahnik K;Linnemann AK;Kang YA;Choi K;Farnham PJ;Bresnick EH
通讯作者：
Bresnick EH
DOI：
10.3324/haematol.2011.054361
发表时间：
2012-06-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Boedoer, Csaba;Renneville, Aline;Owen, Carolyn
通讯作者：
Owen, Carolyn
影响因子：
20.3
作者：
Frisan, Emilie;Vandekerckhove, Julie;Fontenay, Michaela
通讯作者：
Fontenay, Michaela
影响因子：
20.3
作者：
Greenberg, Peter L.;Tuechler, Heinz;Haase, Detlef
通讯作者：
Haase, Detlef
影响因子：
20.3
作者：
Tsai, FY;Orkin, SH
通讯作者：
Orkin, SH