文章：

SAMHD1在T细胞幼淋巴细胞白血病中反复突变

SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia

原文发布日期：2018-01-19

DOI: 10.1038/s41408-017-0036-5

类型: Article

开放获取: 是

英文摘要：

T-cell prolymphocytic leukemia (T-PLL) is an aggressive malignancy with a median survival of the patients of less than two years. Besides characteristic chromosomal translocations, frequent mutations affect the ATM gene, JAK/STAT pathway members, and epigenetic regulators. We here performed a targeted mutation analysis for 40 genes selected from a RNA sequencing of 10 T-PLL in a collection of 28 T-PLL, and an exome analysis of five further cases. Nonsynonymous mutations were identified in 30 of the 40 genes, 18 being recurrently mutated. We identified recurrently mutated genes previously unknown to be mutated in T-PLL, which are SAMHD1, HERC1, HERC2, PRDM2, PARP10, PTPRC, and FOXP1. SAMHD1 regulates cellular deoxynucleotide levels and acts as a potential tumor suppressor in other leukemias. We observed destructive mutations in 18% of cases as well as deletions in two further cases. Taken together, we identified additional genes involved in JAK/STAT signaling (PTPRC), epigenetic regulation (PRDM2), or DNA damage repair (SAMHD1, PARP10, HERC1, and HERC2) as being recurrently mutated in T-PLL. Thus, our study considerably extends the picture of pathways involved in molecular pathogenesis of T-PLL and identifies the tumor suppressor gene SAMHD1 with ~20% of T-PLL affected by destructive lesions likely as major player in T-PLL pathogenesis.

摘要翻译： 

T细胞幼淋巴细胞白血病（T-PLL）是一种侵袭性恶性疾病，患者中位生存期不足两年。除特征性染色体易位外，ATM基因、JAK/STAT通路成员及表观遗传调控因子常出现突变。本研究通过对28例T-PLL样本（其中10例进行RNA测序）进行40个基因的靶向突变分析，并对另外5例进行外显子组分析。在40个基因中鉴定出30个存在非同义突变，其中18个为复发性突变。我们发现了T-PLL中此前未知的复发性突变基因，包括SAMHD1、HERC1、HERC2、PRDM2、PARP10、PTPRC和FOXP1。SAMHD1可调节细胞脱氧核苷酸水平，在其他白血病中作为潜在抑癌基因发挥作用。我们在18%的病例中观察到破坏性突变，并在另外两例中发现缺失突变。综上所述，我们确定了参与JAK/STAT信号传导（PTPRC）、表观遗传调控（PRDM2）或DNA损伤修复（SAMHD1、PARP10、HERC1和HERC2）的新基因在T-PLL中发生复发性突变。因此，本研究显著拓展了T-PLL分子发病机制所涉及的通路图谱，并确定抑癌基因SAMHD1（约20%的T-PLL病例存在该基因破坏性病变）可能是T-PLL发病机制中的重要参与者。

原文链接：

SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia