Somatic SETBP1 mutations in myeloid malignancies.
Somatic SETBP1 mutations in myeloid malignancies.
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DOI：
10.1038/ng.2696
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发表时间：
2013-08
期刊：
影响因子：
30.8
通讯作者：
Maciejewski, Jaroslaw P.
中科院分区：
文献类型：
--
作者：
Makishima, Hideki;Yoshida, Kenichi;Nhu Nguyen;Przychodzen, Bartlomiej;Sanada, Masashi;Okuno, Yusuke;Ng, Kwok Peng;Gudmundsson, Kristbjorn O.;Vishwakarma, Bandana A.;Jerez, Andres;Gomez-Segui, Ines;Takahashi, Mariko;Shiraishi, Yuichi;Nagata, Yasunobu;Guinta, Kathryn;Mori, Hiraku;Sekeres, Mikkael A.;Chiba, Kenichi;Tanaka, Hiroko;Muramatsu, Hideki;Sakaguchi, Hirotoshi;Paquette, Ronald L.;McDevitt, Michael A.;Kojima, Seiji;Saunthararajah, Yogen;Miyano, Satoru;Shih, Lee-Yung;Du, Yang;Ogawa, Seishi;Maciejewski, Jaroslaw P.
在这里，我们报告全外显子组测序的个人与各种骨髓恶性肿瘤，并确定复发性体细胞突变inSETBP 1，与最近的报告一致的非典型慢性粒细胞白血病（aCML）。在17%的继发性急性髓性白血病（sAML）和15%的慢性粒单核细胞白血病（CMML）病例中检测到编码Asp 868、Ser 869、Gly 870、Ile 871和Asp 880变化的紧密定位的体细胞SETBP 1突变，这些突变与Schinzel-Giedion综合征（SGS）的种系突变相匹配。这些来自深度测序的结果证明了比用常规测序方法报道的更高的突变检测率。突变病例与高龄和单体7/缺失7 q（-7/del（7 q））相关，构成不良预后因素。连续收集的样本分析表明，SETBP 1突变是在白血病演变过程中获得的。与野生型Setbp 1转导的细胞相比，小鼠骨髓祖细胞的永生化表现出增强的增殖能力。SETBP 1的体细胞突变似乎导致功能获得，与髓系白血病转化相关，并在骨髓增生异常综合征（MDS）和CMML中传达不良预后。
Here we report whole-exome sequencing of individuals with various myeloid malignancies and identify recurrent somatic mutations inSETBP1, consistent with a recent report on atypical chronic myeloid leukemia (aCML). Closely positioned somaticSETBP1mutations encoding changes in Asp868, Ser869, Gly870, Ile871 and Asp880, which match germline mutations in Schinzel-Giedion syndrome (SGS), were detected in 17% of secondary acute myeloid leukemias (sAML) and 15% of chronic myelomonocytic leukemia (CMML) cases. These results from deep sequencing demonstrate a higher mutational detection rate than reported with conventional sequencing methodology,,. Mutant cases were associated with advanced age and monosomy 7/deletion 7q (–7/del(7q)) constituting poor prognostic factors. Analysis of serially collected samples indicated thatSETBP1mutations were acquired during leukemic evolution. Transduction with mutantSetbp1led to the immortalization of mouse myeloid progenitors that showed enhanced proliferative capacity compared to cells transduced with wild-typeSetbp1. Somatic mutations ofSETBP1seem to cause gain of function, are associated with myeloid leukemic transformation and convey poor prognosis in myelodysplastic syndromes (MDS) and CMML.
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影响因子：
20.3
作者：
Osato, M;Asou, N;Ito, Y
通讯作者：
Ito, Y
影响因子：
30.8
作者：
Hoischen, Alexander;van Bon, Bregje W. M.;Veltman, Joris A.
通讯作者：
Veltman, Joris A.
影响因子：
23.9
作者：
Goyama, Susumu;Yamamoto, Go;Kurokawa, Mineo
通讯作者：
Kurokawa, Mineo
DOI：
10.1073/pnas.85.5.1629
发表时间：
1988-03-01
影响因子：
11.1
作者：
FARR, CJ;SAIKI, RK;MARSHALL, CJ
通讯作者：
MARSHALL, CJ
影响因子：
20.3
作者：
Greenberg, P;Cox, C;Bennett, J
通讯作者：
Bennett, J