The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants
Rio-Machin, Ana (Queen Mary University of London)
Vulliamy, Tom (Queen Mary University of London)
Hug, Nele (University of Edinburgh)
Walne, Amanda (Queen Mary University of London)
Tawana, Kiran (Addenbrookes Hospital (Cambridge, Regne Unit))
Cardoso, Shirleny (Queen Mary University of London)
Ellison, Alicia (Queen Mary University of London)
Pontikos, Nikolas (Queen Mary University of London)
Wang, Jun (Queen Mary University of London)
Tummala, Hemanth (Queen Mary University of London)
Al Seraihi, Ahad Fahad H. (Queen Mary University of London)
Alnajar, Jenna (Queen Mary University of London)
Bewicke-Copley, Findlay (Queen Mary University of London)
Armes, Hannah (Queen Mary University of London)
Barnett, Michael (University of British Columbia)
Bloor, Adrian (Christie Hospital)
Bödör, Csaba (Semmelweis University)
Bowen, David (St James's University Hospital)
Fenaux, Pierre (Université Paris)
Green, Andrew (Our Lady's Children's Hospital)
Hallahan, Andrew (Queensland Children's Hospital (Austràlia))
Hjorth-Hansen, Henrik (St Norwegian University of Science and Technology)
Hossain, Upal (Barts NHS Trust)
Killick, Sally (Royal Bournemouth General Hospital (Dorset, Regne Unit))
Lawson, Sarah (Birmingham Children's Hospital)
Layton, Mark (Hammersmith Hospital (Londres))
Male, Alison M. (Great Ormond Street Hospital for Children (Londres))
Marsh, Judith (King's College Hospital NHS Foundation Trust)
Mehta, Priyanka (University Hospitals Bristol NHS Foundation Trust)
Mous, Rogier (Universitair Medisch Centrum Utrecht)
Nomdedeu, Josep (Institut d'Investigació Biomèdica Sant Pau)
Owen, Carolyn (Foothills Medical Centre)
Pavlu, Jiri (Hammersmith Hospital (Londres))
Payne, Elspeth M. (University College London)
Protheroe, Rachel E. (University Hospitals Bristol NHS Foundation Trust)
Preudhomme, Claude (Universitaire de Lille. Jean-Pierre Aubert Research Center)
Pujol-Moix, Nuria (Institut d'Investigació Biomèdica Sant Pau)
Renneville, Aline (Broad Institute of MIT and Harvard)
Russell, Nigel (Nottingham University Hospitals NHS Trust (Regne Unit))
Saggar, Anand (St George's Hospital Medical School)
Sciuccati, Gabriela (Hospital de Pediatría "Prof. Dr. Juan P. Garrahan")
Taussig, David (Royal Marsden Hospital (Regne Unit))
Toze, Cynthia L. (University of British Columbia)
Uyttebroeck, Anne (University Hospitals Leuven (Bèlgica))
Vandenberghe, Peter (University Hospitals Leuven (Bèlgica))
Schlegelberger, Brigitte (Medizinische Hochschule Hannover)
Ripperger, Tim (Medizinische Hochschule Hannover)
Steinemann, Doris (Medizinische Hochschule Hannover)
Wu, John (British Columbia Children's Hospital (Vancouver, Canadà))
Mason, Joanne (Birmingham Women's NHS Foundation Trust)
Page, Paula (Birmingham Women's NHS Foundation Trust)
Akiki, Susanna (Qatar Rehabilitation Institute)
Reay, Kim (Birmingham Women's NHS Foundation Trust)
Cavenagh, Jamie D. (Barts NHS Trust)
Plagnol, Vincent (University College London)
Caceres, Javier F. (University of Edinburgh)
Fitzgibbon, Jude (Queen Mary University of London)
Dokal, Inderjeet (Barts Health NHS Trust)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	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. Familial myeloid malignancies have recently been classified as separate disease entities. Here, using whole-exome sequencing of affected pedigrees - the authors highlight genetic variants associated with these conditions.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Cancer genomics ; Acute myeloid leukaemia
Published in:	Nature communications, Vol. 11 (february 2020) , ISSN 2041-1723

DOI: 10.1038/s41467-020-14829-5
PMID: 32098966

12 p, 1.1 MB

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Articles > Research articles
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