The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants
Al, Seraihi, AFH
AffiliationCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK
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AbstractThe inclusion of familial myeloid malignancies as a separate disease entity in the revised WHO classification has renewed efforts to improve the recognition and management of this group of at risk individuals. Here we report a cohort of 86 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) families with 49 harboring germline variants in 16 previously defined loci (57%). Whole exome sequencing in a further 37 uncharacterized families (43%) allowed us to rationalize 65 new candidate loci, including genes mutated in rare hematological syndromes (ADA, GP6, IL17RA, PRF1 and SEC23B), reported in prior MDS/AML or inherited bone marrow failure series (DNAH9, NAPRT1 and SH2B3) or variants at novel loci (DHX34) that appear specific to inherited forms of myeloid malignancies. Altogether, our series of MDS/AML families offer novel insights into the etiology of myeloid malignancies and provide a framework to prioritize variants for inclusion into routine diagnostics and patient management.
CitationRio-Machin A, Vulliamy T, Hug N, Walne A, Tawana K, Cardoso S, et al. The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants. Nat Commun. 2020;11:1044.
- Genomic analysis of germ line and somatic variants in familial myelodysplasia/acute myeloid leukemia.
- Authors: Churpek JE, Pyrtel K, Kanchi KL, Shao J, Koboldt D, Miller CA, Shen D, Fulton R, O'Laughlin M, Fronick C, Pusic I, Uy GL, Braunstein EM, Levis M, Ross J, Elliott K, Heath S, Jiang A, Westervelt P, DiPersio JF, Link DC, Walter MJ, Welch J, Wilson R, Ley TJ, Godley LA, Graubert TA
- Issue date: 2015 Nov 26
- Familial myelodysplasia and acute myeloid leukaemia--a review.
- Authors: Owen C, Barnett M, Fitzgibbon J
- Issue date: 2008 Jan
- Universal genetic testing for inherited susceptibility in children and adults with myelodysplastic syndrome and acute myeloid leukemia: are we there yet?
- Authors: Tawana K, Drazer MW, Churpek JE
- Issue date: 2018 Jul
- Familial Acute Myeloid Leukemia and Myelodysplasia in Hungary.
- Authors: Király AP, Kállay K, Gángó A, Kellner Á, Egyed M, Szőke A, Kiss R, Vályi-Nagy I, Csomor J, Matolcsy A, Bödör C
- Issue date: 2018 Jan
- Germline DDX41 mutations define a significant entity within adult MDS/AML patients.
- Authors: Sébert M, Passet M, Raimbault A, Rahmé R, Raffoux E, Sicre de Fontbrune F, Cerrano M, Quentin S, Vasquez N, Da Costa M, Boissel N, Dombret H, Peffault de Latour R, Socié G, Itzykson R, Fenaux P, Soulier J, Adès L, Clappier E
- Issue date: 2019 Oct 24