Polprasert Chantana, Schulze Isabell, Sekeres Mikkael A, Makishima Hideki, Przychodzen Bartlomiej, Hosono Naoko, Singh Jarnail, Padgett Richard A, Gu Xiaorong, Phillips James G, Clemente Michael, Parker Yvonne, Lindner Daniel, Dienes Brittney, Jankowsky Eckhard, Saunthararajah Yogen, Du Yang, Oakley Kevin, Nguyen Nhu, Mukherjee Sudipto, Pabst Caroline, Godley Lucy A, Churpek Jane E, Pollyea Daniel A, Krug Utz, Berdel Wolfgang E, Klein Hans-Ulrich, Dugas Martin, Shiraishi Yuichi, Chiba Kenichi, Tanaka Hiroko, Miyano Satoru, Yoshida Kenichi, Ogawa Seishi, Müller-Tidow Carsten, Maciejewski Jaroslaw P
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland, OH 44195, USA; Department of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Hematology and Oncology, University of Halle, Halle 06108, Germany; Department of Hematology and Oncology, University of Muenster, Muenster 48149, Germany.
Cancer Cell. 2015 May 11;27(5):658-70. doi: 10.1016/j.ccell.2015.03.017. Epub 2015 Apr 23.
Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. Moreover, corresponding deletions on 5q35.3 present in 6% of cases led to haploinsufficient DDX41 expression. DDX41 lesions caused altered pre-mRNA splicing and RNA processing. DDX41 is exemplary of other RNA helicase genes also affected by somatic mutations, suggesting that they constitute a family of tumor suppressor genes.
大多数成人髓系肿瘤病例通常被认为是散发性的。在此，我们描述了一种由DEAD/H-box解旋酶基因DDX41的种系突变引起的成人家族性急性髓系白血病（AML）综合征。在散发性髓系肿瘤病例中也发现DDX41受到体细胞突变的影响，并且在50%的种系DDX41突变患者中以双等位基因方式受到影响。此外，6%的病例中存在的5q35.3相应缺失导致DDX41表达单倍体不足。DDX41损伤导致前体mRNA剪接和RNA加工改变。DDX41是其他也受体细胞突变影响的RNA解旋酶基因的典型代表，表明它们构成了一个肿瘤抑制基因家族。
