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The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants
- Source :
- Nature Communications, r-IIB SANT PAU: Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, Institut dInvestigació Biomèdica Sant Pau (IIB Sant Pau), Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona, Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020), Rio-machin, A, Vulliamy, T, Hug, N, Walne, A, Tawana, K, Cardoso, S, Ellison, A, Pontikos, N, Wang, J, Tummala, H, Al Seraihi, A F, Alnajar, J, Bewicke-Copley, F, Armes, H, Barnett, M, Bloor, A, Bodor, C, Bowen, D, Fenaux, P, Green, A, Hallahan, A, Hjorth-Hansen, H, Hossain, U, Killick, S, Lawson, S, Layton, M, Male, A M, Marsh, J, Mehta, P, Mous, R, Nomdedeu, J F, Owen, C, Pavlu, J, Payne, E, Protheroe, R, Predhomme, C, Pujol-Moix, N, Renneville, A, Russell, N, Saggar, A, Sciuccati, G, Taussig, D, Toze, C, Uyttebroeck, A, Vandenberghe, P, Schlegelberger, B, Ripperger, T, Steinemann, D, Wu, J, Mason, J, Page, P, El Akiki, S, Reay, K, Cavenagh, J D, Plagnol, V, Caceres, J F, Fitzgibbon, J & Dokal, I 2020, ' The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants ', Nature Communications . https://doi.org/10.1038/s41467-020-14829-5, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname
- Publication Year :
- 2020
- Publisher :
- NATURE PORTFOLIO, 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.<br />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.
- Subjects :
- 0301 basic medicine
Myeloid
Adenosine Deaminase
Vesicular Transport Proteins
General Physics and Astronomy
DYSKERATOSIS-CONGENITA
Whole Exome Sequencing
Cohort Studies
0302 clinical medicine
hemic and lymphatic diseases
CEBPA
Cancer genomics
RUNX1 MUTATIONS
lcsh:Science
Exome sequencing
MYELODYSPLASTIC SYNDROME
Genetics
Multidisciplinary
Receptors, Interleukin-17
Myeloid leukemia
SAMD9L MUTATIONS CAUSE
Pedigree
Multidisciplinary Sciences
Leukemia
Leukemia, Myeloid, Acute
medicine.anatomical_structure
030220 oncology & carcinogenesis
Science & Technology - Other Topics
RNA Helicases
Platelet disorder
Science
LINE
ACUTE MYELOID-LEUKEMIA
Platelet Membrane Glycoproteins
Biology
General Biochemistry, Genetics and Molecular Biology
Article
Acute myeloid leukaemia
03 medical and health sciences
Germline mutation
PLATELET DISORDER
Exome Sequencing
medicine
Humans
MECHANISTIC INSIGHTS
Germ-Line Mutation
Adaptor Proteins, Signal Transducing
Science & Technology
Perforin
Myelodysplastic syndromes
General Chemistry
Axonemal Dyneins
medicine.disease
Nonsense Mediated mRNA Decay
SELF-RENEWAL
030104 developmental biology
Myelodysplastic Syndromes
lcsh:Q
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, r-IIB SANT PAU: Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, Institut dInvestigació Biomèdica Sant Pau (IIB Sant Pau), Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona, Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020), Rio-machin, A, Vulliamy, T, Hug, N, Walne, A, Tawana, K, Cardoso, S, Ellison, A, Pontikos, N, Wang, J, Tummala, H, Al Seraihi, A F, Alnajar, J, Bewicke-Copley, F, Armes, H, Barnett, M, Bloor, A, Bodor, C, Bowen, D, Fenaux, P, Green, A, Hallahan, A, Hjorth-Hansen, H, Hossain, U, Killick, S, Lawson, S, Layton, M, Male, A M, Marsh, J, Mehta, P, Mous, R, Nomdedeu, J F, Owen, C, Pavlu, J, Payne, E, Protheroe, R, Predhomme, C, Pujol-Moix, N, Renneville, A, Russell, N, Saggar, A, Sciuccati, G, Taussig, D, Toze, C, Uyttebroeck, A, Vandenberghe, P, Schlegelberger, B, Ripperger, T, Steinemann, D, Wu, J, Mason, J, Page, P, El Akiki, S, Reay, K, Cavenagh, J D, Plagnol, V, Caceres, J F, Fitzgibbon, J & Dokal, I 2020, ' The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants ', Nature Communications . https://doi.org/10.1038/s41467-020-14829-5, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname
- Accession number :
- edsair.doi.dedup.....43441adab8bb9b0f13c4acc683573c5e