DDX41 mutations in myeloid neoplasms are associated with male gender, TP53 mutations and high-risk disease.

Autor: Quesada AE; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Routbort MJ; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., DiNardo CD; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas., Bueso-Ramos CE; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Kanagal-Shamanna R; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Khoury JD; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Thakral B; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Zuo Z; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Yin CC; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Loghavi S; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Ok CY; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Wang SA; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Tang Z; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Bannon SA; Department of Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas., Benton CB; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas., Garcia-Manero G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas., Kantarjian H; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas., Luthra R; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Medeiros LJ; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Patel KP; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2019 Jul; Vol. 94 (7), pp. 757-766. Date of Electronic Publication: 2019 May 07.
DOI: 10.1002/ajh.25486
Abstrakt: Myeloid neoplasms with germline DDX41 mutations have been incorporated into the 2017 WHO classification. Limited studies describing the clinicopathologic features and mutation profile are available. We searched for myeloid neoplasms with a DDX41 gene mutation tested by an 81-gene next-generation sequencing panel over a 7-month period. We identified 34 patients with myeloid neoplasms with DDX41 abnormalities; 26 (76%) men and 8 women (24%) [median age, 70 years], 20 acute myeloid leukemia (AML), 10 myelodysplastic syndrome (MDS), 1 chronic myelomonocytic leukemia (CMML) and 3 myeloproliferative neoplasms (MPN). Fifty-nine DDX41 variants were detected: 27 (46%) appeared somatic and 32 (54%) were presumably germline mutations. The majority of presumed germline mutations were upstream of the Helicase 2 domain (93%) and involved loss of the start codon (30%). The majority of somatic mutations were within the Helicase 2 domain (78%), with the missense mutation p.R525H being most common (67%). There was a significant difference in the location of germline or somatic mutations (P < .0001). Concomitant mutations were detected involving 19 genes, but only TP53 (n = 11, 32%), ASXL1 (n = 8, 24%), and JAK2 (n = 4, 12%) were recurrent. Twenty (59%) patients showed diploid cytogenetics. Twenty-three (68%) patients presented with AML or MDS-EB-2, suggesting an association with high-grade myeloid neoplasm. Patients with myeloid neoplasms carrying DDX41 mutations show male predominance (3:1), higher age at presentation, association with TP53 mutations, and association with high-grade myeloid neoplasms in our cohort at a referral cancer center setting. These findings support the recognition of myeloid neoplasms with DDX41 mutation as unique, need for germline confirmation, and further assessment of family members.
(© 2019 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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