Next-Generation Sequencing of DDX41 in Myeloid Neoplasms Leads to Increased Detection of Germline Alterations.

Autor:	Bannon SA; Department of Clinical Cancer Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Routbort MJ; Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Montalban-Bravo G; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Mehta RS; Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Jelloul FZ; Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Takahashi K; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Daver N; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Oran B; Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Pemmaraju N; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Borthakur G; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Naqvi K; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Issa G; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Sasaki K; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Alvarado Y; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Kadia TM; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Konopleva M; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Shamanna RK; Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Khoury JD; Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Ravandi F; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Champlin R; Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Kantarjian HM; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Bhalla K; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Garcia-Manero G; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., Patel KP; Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States., DiNardo CD; Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2021 Jan 28; Vol. 10, pp. 582213. Date of Electronic Publication: 2021 Jan 28 (Print Publication: 2020).
DOI:	10.3389/fonc.2020.582213
Abstrakt:	Previously considered rare, inherited hematologic malignancies are increasingly identified. Germline mutations in the RNA helicase DDX41 predispose to increased lifetime risks of myeloid neoplasms with disease often occurring later in life which presents challenges for germline recognition. To improve identification of germline DDX41 , individuals presenting with ≥1 DDX41 alteration on an institutional MDS/AML next-generation sequencing based panel with at least one at >40% variant allele frequency were flagged for review and genetic counseling referral. Of 5,801 individuals, 90 (1.5%) had ≥1 DDX41 mutation(s) identified. Thirty-eight (42%) patients with a median age of 66 years were referred for genetic counseling; thirty-one were male (81.5%). Thirty-five (92%) referred patients elected to pursue germline evaluation and in 33/35 (94%) a germline DDX41 variant was confirmed. Twenty-two patients (66%) with germline variants reported antecedent cytopenias, seven (21%) had a prior history of malignancy, and twenty-seven (82%) reported a family history of cancer. Predictive genetic testing for healthy family members under consideration as stem cell transplant donors was successfully performed in 11 family members, taking an average of 15 days. Near-heterozygous DDX41 mutations identified on next-generation sequencing, particularly nonsense/frameshift variants or those at recurrent germline "hot spots" are highly suggestive of a germline mutation. Next-generation sequencing screening is a feasible tool to screen unselected myeloid neoplasms for germline DDX41 mutations, enabling timely and appropriate care. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CH declared a past co-authorship with one of the authors CD to the handling editor. (Copyright © 2021 Bannon, Routbort, Montalban-Bravo, Mehta, Jelloul, Takahashi, Daver, Oran, Pemmaraju, Borthakur, Naqvi, Issa, Sasaki, Alvarado, Kadia, Konopleva, Shamanna, Khoury, Ravandi, Champlin, Kantarjian, Bhalla, Garcia-Manero, Patel and DiNardo.)
Databáze:	MEDLINE
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