The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.
Authors
Rio-Machin, AnaVulliamy, Tom
Hug, Nele
Walne, Amanda
Tawana, Kiran
Cardoso, Shirleny
Ellison, Alicia
Pontikos, Nikolas
Wang, Jun
Tummala, Hemanth
Al Seraihi, Ahad Fahad H
Alnajar, Jenna
Bewicke-Copley, Findlay
Armes, Hannah
Barnett, Michael
Bloor, Adrian
Bödör, Csaba
Bowen, David
Fenaux, Pierre
Green, Andrew
Hallahan, Andrew
Hjorth-Hansen, Henrik
Hossain, Upal
Killick, Sally
Lawson, Sarah
Layton, Mark
Male, Alison M
Marsh, Judith
Mehta, Priyanka
Mous, Rogier
Nomdedéu, Josep F
Owen, Carolyn
Pavlu, Jiri
Payne, Elspeth M
Protheroe, Rachel E
Preudhomme, Claude
Pujol-Moix, Nuria
Renneville, Aline
Russell, Nigel
Saggar, Anand
Sciuccati, Gabriela
Taussig, David
Toze, Cynthia L
Uyttebroeck, Anne
Vandenberghe, Peter
Schlegelberger, Brigitte
Ripperger, Tim
Steinemann, Doris
Wu, John
Mason, Joanne
Page, Paula
Akiki, Susanna
Reay, Kim
Cavenagh, Jamie D
Plagnol, Vincent
Caceres, Javier F
Fitzgibbon, Jude
Dokal, Inderjeet
Issue Date
2020-02-25Keywords
LEUKAEMIAGENETIC FACTORS
RISK FACTORS
HEREDITY
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Nature communicationsDOI
10.1038/s41467-020-14829-5PubMed ID
32098966Abstract
he 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.Item Type
ArticleOther
Language
enEISSN
2041-1723ae974a485f413a2113503eed53cd6c53
10.1038/s41467-020-14829-5
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