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The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants
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 (M...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042299/ https://www.ncbi.nlm.nih.gov/pubmed/32098966 http://dx.doi.org/10.1038/s41467-020-14829-5 |
| _version_ | 1783501282405777408 |
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| author | Rio-Machin, Ana Vulliamy, 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 |
| author_facet | Rio-Machin, Ana Vulliamy, 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 |
| author_sort | Rio-Machin, Ana |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-7042299 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-70422992020-03-04 The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants Rio-Machin, Ana Vulliamy, 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 Nat Commun Article 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. Nature Publishing Group UK 2020-02-25 /pmc/articles/PMC7042299/ /pubmed/32098966 http://dx.doi.org/10.1038/s41467-020-14829-5 Text en © The Author(s) 2020 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, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Rio-Machin, Ana Vulliamy, 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 The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants |
| title | The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants |
| title_full | The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants |
| title_fullStr | The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants |
| title_full_unstemmed | The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants |
| title_short | The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants |
| title_sort | complex genetic landscape of familial mds and aml reveals pathogenic germline variants |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042299/ https://www.ncbi.nlm.nih.gov/pubmed/32098966 http://dx.doi.org/10.1038/s41467-020-14829-5 |
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