The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants
Authors
Rio-Machin, AVulliamy, T
Hug, N
Walne, A
Tawana, K
Cardoso, S
Ellison, A
Pontikos, N
Wang, J
Tummala, H
Al, Seraihi, AFH
Alnajar, J
Bewicke-Copley, F
Armes, H
Barnett, M
Bloor, Adrian
Bodor, C
Bowen, D
Fenaux, P
Green, A
Hallahan, A
Hjorth-Hansen, H
Hossain, U
Killick, S
Lawson, S
Layton, M
Male, AM
Marsh, J
Mehta, P
Mous, R
Nomdedeu, JF
Owen, C
Pavlu, J
Payne, EM
Protheroe, RE
Preudhomme, C
Pujol-Moix, N
Renneville, A
Russell, N
Saggar, A
Sciuccati, G
Taussig, D
Toze, CL
Uyttebroeck, A
Vandenberghe, P
Schlegelberger, B
Ripperger, T
Steinemann, D
Wu, J
Mason, J
Page, P
Akiki, S
Reay, K
Cavenagh, JD
Plagnol, V
Caceres, JF
Fitzgibbon, J
Dokal, I
Affiliation
Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UKIssue Date
2020
Metadata
Show full item recordAbstract
The 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.Citation
Rio-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.Journal
Nature CommunicationsDOI
10.1038/s41467-020-14829-5PubMed ID
32098966Additional Links
https://dx.doi.org/10.1038/s41467-020-14829-5Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41467-020-14829-5