Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms
Menée initialement à partir d'échantillons de sang ou de moelle osseuse prélevés sur 8 patients appartenant à des familles affectées par une leucémie myéloïde aiguë, puis sur une cohorte de 840 patients et à partir de données issues du projet "The Cancer Genome Atlas", cette étude identifie des mutations constitutionnelles du gène DDX41 associées au risque de syndromes myélodysplasiques et de leucémie myéloide aiguë
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.
Cancer Cell 2015