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Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors
Metastatic uveal melanoma is a deadly disease with no proven standard of care. Here we present a metastatic uveal melanoma patient with an exceptional high sensitivity to a PD-1 inhibitor associated with outlier CpG>TpG mutation burden, MBD4 germline deleterious mutation, and somatic MBD4 inactiv...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2018
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951831/ https://www.ncbi.nlm.nih.gov/pubmed/29760383 http://dx.doi.org/10.1038/s41467-018-04322-5 |
| _version_ | 1783323077746098176 |
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| author | Rodrigues, Manuel Mobuchon, Lenha Houy, Alexandre Fiévet, Alice Gardrat, Sophie Barnhill, Raymond L. Popova, Tatiana Servois, Vincent Rampanou, Aurore Mouton, Aurore Dayot, Stéphane Raynal, Virginie Galut, Michèle Putterman, Marc Tick, Sarah Cassoux, Nathalie Roman-Roman, Sergio Bidard, François-Clément Lantz, Olivier Mariani, Pascale Piperno-Neumann, Sophie Stern, Marc-Henri |
| author_facet | Rodrigues, Manuel Mobuchon, Lenha Houy, Alexandre Fiévet, Alice Gardrat, Sophie Barnhill, Raymond L. Popova, Tatiana Servois, Vincent Rampanou, Aurore Mouton, Aurore Dayot, Stéphane Raynal, Virginie Galut, Michèle Putterman, Marc Tick, Sarah Cassoux, Nathalie Roman-Roman, Sergio Bidard, François-Clément Lantz, Olivier Mariani, Pascale Piperno-Neumann, Sophie Stern, Marc-Henri |
| author_sort | Rodrigues, Manuel |
| collection | PubMed |
| description | Metastatic uveal melanoma is a deadly disease with no proven standard of care. Here we present a metastatic uveal melanoma patient with an exceptional high sensitivity to a PD-1 inhibitor associated with outlier CpG>TpG mutation burden, MBD4 germline deleterious mutation, and somatic MBD4 inactivation in the tumor. We identify additional tumors in The Cancer Genome Atlas (TCGA) cohorts with similar hypermutator profiles in patients carrying germline deleterious MBD4 mutations and somatic loss of heterozygosity. This MBD4-related hypermutator phenotype may explain unexpected responses to immune checkpoint inhibitors. |
| format | Online Article Text |
| id | pubmed-5951831 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-59518312018-05-16 Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors Rodrigues, Manuel Mobuchon, Lenha Houy, Alexandre Fiévet, Alice Gardrat, Sophie Barnhill, Raymond L. Popova, Tatiana Servois, Vincent Rampanou, Aurore Mouton, Aurore Dayot, Stéphane Raynal, Virginie Galut, Michèle Putterman, Marc Tick, Sarah Cassoux, Nathalie Roman-Roman, Sergio Bidard, François-Clément Lantz, Olivier Mariani, Pascale Piperno-Neumann, Sophie Stern, Marc-Henri Nat Commun Article Metastatic uveal melanoma is a deadly disease with no proven standard of care. Here we present a metastatic uveal melanoma patient with an exceptional high sensitivity to a PD-1 inhibitor associated with outlier CpG>TpG mutation burden, MBD4 germline deleterious mutation, and somatic MBD4 inactivation in the tumor. We identify additional tumors in The Cancer Genome Atlas (TCGA) cohorts with similar hypermutator profiles in patients carrying germline deleterious MBD4 mutations and somatic loss of heterozygosity. This MBD4-related hypermutator phenotype may explain unexpected responses to immune checkpoint inhibitors. Nature Publishing Group UK 2018-05-14 /pmc/articles/PMC5951831/ /pubmed/29760383 http://dx.doi.org/10.1038/s41467-018-04322-5 Text en © The Author(s) 2018 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 Rodrigues, Manuel Mobuchon, Lenha Houy, Alexandre Fiévet, Alice Gardrat, Sophie Barnhill, Raymond L. Popova, Tatiana Servois, Vincent Rampanou, Aurore Mouton, Aurore Dayot, Stéphane Raynal, Virginie Galut, Michèle Putterman, Marc Tick, Sarah Cassoux, Nathalie Roman-Roman, Sergio Bidard, François-Clément Lantz, Olivier Mariani, Pascale Piperno-Neumann, Sophie Stern, Marc-Henri Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors |
| title | Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors |
| title_full | Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors |
| title_fullStr | Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors |
| title_full_unstemmed | Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors |
| title_short | Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors |
| title_sort | outlier response to anti-pd1 in uveal melanoma reveals germline mbd4 mutations in hypermutated tumors |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951831/ https://www.ncbi.nlm.nih.gov/pubmed/29760383 http://dx.doi.org/10.1038/s41467-018-04322-5 |
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