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TET2 和 JAK2 突变的克隆分析表明,TET2 可能是骨髓增殖性肿瘤进展过程中的晚期事件。

Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms.

机构信息

Department of Biomedicine, Experimental Hematology, University Hospital Basel, Hebelstr 20, 4031 Basel, Switzerland.

出版信息

Blood. 2010 Mar 11;115(10):2003-7. doi: 10.1182/blood-2009-09-245381. Epub 2010 Jan 8.

Abstract

Somatic mutations in TET2 occur in patients with myeloproliferative neoplasms and other hematologic malignancies. It has been suggested that TET2 is a tumor suppressor gene and mutations in TET2 precede the acquisition of JAK2-V617F. To examine the order of events, we performed colony assays and genotyped TET2 and JAK2 in individual colonies. In 4 of 8 myeloproliferative neoplasm patients, we found that some colonies with mutated TET2 carried wild-type JAK2, whereas others were JAK2-V617F positive, indicating that TET2 occurred before JAK2-V617F. One of these patients carried a germline TET2 mutation. However, in 2 other patients, we obtained data compatible with the opposite order of events, with JAK2 exon 12 mutation preceding TET2 mutation in one case. Finally, in 2 of 8 patients, the TET2 and JAK2-V617F mutations defined 2 separate clones. The lack of a strict temporal order of occurrence makes it unlikely that mutations in TET2 represent a predisposing event for acquiring mutations in JAK2.

摘要

TET2 体细胞突变发生于骨髓增殖性肿瘤(MPN)和其他血液恶性肿瘤患者中。目前认为 TET2 是一种抑癌基因,TET2 突变发生于 JAK2-V617F 获得之前。为了研究事件发生的先后顺序,我们对单个集落进行了集落形成实验和 TET2、JAK2 基因型分析。在 8 例 MPN 患者中,我们发现 4 例存在 TET2 突变的集落中有些携带有野生型 JAK2,而另一些则为 JAK2-V617F 阳性,这表明 TET2 突变发生于 JAK2-V617F 之前。其中 1 例患者携带有 TET2 种系突变。然而,在另外 2 例患者中,我们得到的数据支持相反的事件发生顺序,在其中 1 例患者中,JAK2 外显子 12 突变先于 TET2 突变。最后,在 8 例患者中的 2 例中,TET2 和 JAK2-V617F 突变定义了 2 个不同的克隆。这种发生时间上的非严格先后顺序使得 TET2 突变不太可能是 JAK2 获得突变的易患事件。

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