Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms.

Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms.

Cancer cell (2015-04-30)

Chantana Polprasert, Isabell Schulze, Mikkael A Sekeres, Hideki Makishima, Bartlomiej Przychodzen, Naoko Hosono, Jarnail Singh, Richard A Padgett, Xiaorong Gu, James G Phillips, Michael Clemente, Yvonne Parker, Daniel Lindner, Brittney Dienes, Eckhard Jankowsky, Yogen Saunthararajah, Yang Du, Kevin Oakley, Nhu Nguyen, Sudipto Mukherjee, Caroline Pabst, Lucy A Godley, Jane E Churpek, Daniel A Pollyea, Utz Krug, Wolfgang E Berdel, Hans-Ulrich Klein, Martin Dugas, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Kenichi Yoshida, Seishi Ogawa, Carsten Müller-Tidow, Jaroslaw P Maciejewski

PMID25920683

摘要

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.