Rio-Machin, A;
Vulliamy, T;
Hug, N;
Walne, A;
Tawana, K;
Cardoso, S;
Ellison, A;
Pontikos, N;
Wang, J;
Tummala, H;
et al.
Rio-Machin, A; Vulliamy, 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, A; Bödör, 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; Nomdedéu, 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
(2020)
The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.
Nat Commun, 11 (1).
p. 1044.
ISSN 2041-1723
https://doi.org/10.1038/s41467-020-14829-5
SGUL Authors: Saggar, Anand Kumar
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.
| Item Type: |
Article
|
| Additional Information: |
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2020 |
| Keywords: |
Adaptor Proteins, Signal Transducing, Adenosine Deaminase, Axonemal Dyneins, Cohort Studies, Germ-Line Mutation, Humans, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Nonsense Mediated mRNA Decay, Pedigree, Perforin, Platelet Membrane Glycoproteins, RNA Helicases, Receptors, Interleukin-17, Vesicular Transport Proteins, Whole Exome Sequencing, Humans, Myelodysplastic Syndromes, Adenosine Deaminase, RNA Helicases, Adaptor Proteins, Signal Transducing, Platelet Membrane Glycoproteins, Vesicular Transport Proteins, Cohort Studies, Pedigree, Germ-Line Mutation, Receptors, Interleukin-17, Leukemia, Myeloid, Acute, Perforin, Axonemal Dyneins, Nonsense Mediated mRNA Decay, Whole Exome Sequencing, MD Multidisciplinary |
| SGUL Research Institute / Research Centre: |
Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE)
Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) > Centre for Biomedical Education (INMEBE) |
| Journal or Publication Title: |
Nat Commun |
| ISSN: |
2041-1723 |
| Language: |
eng |
| Dates: |
| Date | Event |
|---|
| 25 February 2020 | Published | | 27 January 2020 | Accepted |
|
| Publisher License: |
Creative Commons: Attribution 4.0 |
| Projects: |
|
| PubMed ID: |
32098966 |
| Web of Science ID: |
WOS:000564284600002 |
 |
Go to PubMed abstract |
| URI: |
https://openaccess.sgul.ac.uk/id/eprint/112494 |
| Publisher's version: |
https://doi.org/10.1038/s41467-020-14829-5 |
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