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http://hdl.handle.net/11434/1569
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DC Field | Value | Language |
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dc.contributor.author | Prince, Miles | - |
dc.contributor.other | Gayden, Tenzin | - |
dc.contributor.other | Sepulveda, Fernando | - |
dc.contributor.other | Khuong-Quang, Dong-Anh | - |
dc.contributor.other | Pratt, Jonathan | - |
dc.contributor.other | Valera, Elvis | - |
dc.contributor.other | Garrigue, Alexandrine | - |
dc.contributor.other | Kelso, Susan | - |
dc.contributor.other | Sicheri, Frank | - |
dc.contributor.other | Mikael, Leonie | - |
dc.contributor.other | Hamel, Nancy | - |
dc.contributor.other | Bajic, Andrea | - |
dc.contributor.other | Dali, Rola | - |
dc.contributor.other | Deshmukh, Shriya | - |
dc.contributor.other | Dervovic, Dzana | - |
dc.contributor.other | Schramek, Daniel | - |
dc.contributor.other | Guerin, Frederic | - |
dc.contributor.other | Taipale, Mikko | - |
dc.contributor.other | Nikbakht, Hamid | - |
dc.contributor.other | Majewski, Jacek | - |
dc.contributor.other | Moshous, Despina | - |
dc.contributor.other | Charlebois, Janie | - |
dc.contributor.other | Abish, Sharon | - |
dc.contributor.other | Bole-Feysot, Christine | - |
dc.contributor.other | Nitschke, Patrick | - |
dc.contributor.other | Bader-Meunier, Brigitte | - |
dc.contributor.other | Mitchell, David | - |
dc.contributor.other | Thieblemont, Catherine | - |
dc.contributor.other | Battistella, Maxime | - |
dc.contributor.other | Gravel, Simon | - |
dc.contributor.other | Nguyen, Van-Hung | - |
dc.contributor.other | Conyers, Rachel | - |
dc.contributor.other | Diana, Jean-Sebastien | - |
dc.contributor.other | McCormack, Chris | - |
dc.contributor.other | Besnard, Marianne | - |
dc.contributor.other | Blanche, Stephane | - |
dc.contributor.other | Ekert, Paul | - |
dc.contributor.other | Fraitag, Sylvie | - |
dc.contributor.other | Foulkes, William | - |
dc.contributor.other | Fischer, Alain | - |
dc.contributor.other | Neven, Benedicte | - |
dc.contributor.other | Michonneau, David | - |
dc.contributor.other | de Saint Basile, Genevieve | - |
dc.contributor.other | Jabado, Nada | - |
dc.date.accessioned | 2018-11-18T23:16:20Z | - |
dc.date.available | 2018-11-18T23:16:20Z | - |
dc.date.issued | 2018-10 | - |
dc.identifier.citation | Nat Genet. 2018 Oct 29 | en_US |
dc.identifier.issn | 1061-4036 | en_US |
dc.identifier.issn | 1546-1718 | en_US |
dc.identifier.uri | http://hdl.handle.net/11434/1569 | - |
dc.description.abstract | Subcutaneous panniculitis-like T cell lymphoma (SPTCL), a non-Hodgkin lymphoma, can be associated with hemophagocytic lymphohistiocytosis (HLH), a life-threatening immune activation that adversely affects survival1,2. T cell immunoglobulin mucin 3 (TIM-3) is a modulator of immune responses expressed on subgroups of T and innate immune cells. We identify in ~60% of SPTCL cases germline, loss-of-function, missense variants altering highly conserved residues of TIM-3, c.245A>G (p.Tyr82Cys) and c.291A>G (p.Ile97Met), each with specific geographic distribution. The variant encoding p.Tyr82Cys TIM-3 occurs on a potential founder chromosome in patients with East Asian and Polynesian ancestry, while p.Ile97Met TIM-3 occurs in patients with European ancestry. Both variants induce protein misfolding and abrogate TIM-3's plasma membrane expression, leading to persistent immune activation and increased production of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, promoting HLH and SPTCL. Our findings highlight HLH-SPTCL as a new genetic entity and identify mutations causing TIM-3 alterations as a causative genetic defect in SPTCL. While HLH-SPTCL patients with mutant TIM-3 benefit from immunomodulation, therapeutic repression of the TIM-3 checkpoint may have adverse consequences. | en_US |
dc.publisher | Nature Publishing Group | en_US |
dc.subject | Subcutaneous Panniculitis-Like T Cell Lymphoma | en_US |
dc.subject | SPTCL | en_US |
dc.subject | Non-Hodgkin Lymphoma | en_US |
dc.subject | Hemophagocytic Lymphohistiocytosis | en_US |
dc.subject | HLH | en_US |
dc.subject | Immune Activation | en_US |
dc.subject | T Cell Immunoglobulin Mucin 3 | en_US |
dc.subject | TIM-3 | en_US |
dc.subject | Immune Responses | en_US |
dc.subject | Immune Cells | en_US |
dc.subject | Gene Mutations | en_US |
dc.subject | Inflammatory Cytokines | en_US |
dc.subject | Immunomodulation | en_US |
dc.subject | Therapeutic Repression | en_US |
dc.title | Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome. | en_US |
dc.type | Journal Article | en_US |
dc.identifier.doi | 10.1038/s41588-018-0251-4 | en_US |
dc.identifier.journaltitle | Nature Genetics | en_US |
dc.description.pubmeduri | https://www.ncbi.nlm.nih.gov/pubmed/30374066 | en_US |
dc.description.affiliates | Department of Human Genetics, McGill University, Montreal, Quebec, Canada. | en_US |
dc.description.affiliates | Laboratory of Normal and Pathological Homeostasis of the Immune System, INSERM U1163, Institut Imagine, and Université Paris Descartes-Sorbonne Paris Cité, Paris, France. | en_US |
dc.description.affiliates | Children's Cancer Center, The Royal Children's Hospital and Murdoch Children's Research Institute, Parkville, Victoria, Australia | en_US |
dc.description.affiliates | Department of Pediatrics, University of Melbourne, Parkville, Victoria, Australia. | en_US |
dc.description.affiliates | Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil. | en_US |
dc.description.affiliates | Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada. | en_US |
dc.description.affiliates | Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. | en_US |
dc.description.affiliates | Cancer Research Program, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada. | en_US |
dc.description.affiliates | Department of Experimental Medicine, McGill University, Montreal, Quebec, Canada. | en_US |
dc.description.affiliates | McGill University and Genome Quebec Innovation Center, Montreal, Quebec, Canada. | en_US |
dc.description.affiliates | Department of Pediatric Immunology and Hematology, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. | en_US |
dc.description.affiliates | Division of Hematology and Oncology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada. | en_US |
dc.description.affiliates | Plateforme de Génomique, Institut Imagine, Paris, France. | en_US |
dc.description.affiliates | Plateforme de Bioinformatique, Université Paris Descartes, Université Sorbonne Paris Cité, Paris, France. | en_US |
dc.description.affiliates | Hematology and Oncology Unit, Saint Louis Hospital, Paris, France. | en_US |
dc.description.affiliates | Paris Diderot University, Université Sorbonne Paris Cité, Paris, France. | en_US |
dc.description.affiliates | Cytology and Pathology Laboratory, Saint Louis Hospital, Paris, France. | en_US |
dc.description.affiliates | Department of Pathology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada. | en_US |
dc.description.affiliates | Department of Surgical Oncology, Peter MacCallum Cancer Institute, University of Melbourne, Melbourne, Victoria, Australia. | en_US |
dc.description.affiliates | Department of Dermatology, St. Vincent's Hospital, Fitzroy, Victoria, Australia. | en_US |
dc.description.affiliates | Department of Medical Oncology, Sir Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria, Australia. | en_US |
dc.description.affiliates | Department of Neonatology, Centre Hospitalier de Polynésie Française, Papeete, French Polynesia. | en_US |
dc.description.affiliates | Department of Anatomy and Cytology/Pathology, Centre Hospitalier Universitaire Paris, Hôpital Necker-Enfants Malades, Paris, France. | en_US |
dc.description.affiliates | Collège de France, Paris, France. | en_US |
dc.description.affiliates | INSERM U1163, Institut Imagine and Université Paris Descartes -Sorbonne Paris Cité, Paris, France. | en_US |
dc.description.affiliates | Hematology and Transplantation Unit, Saint Louis Hospital, Paris, France. | en_US |
dc.description.affiliates | Laboratory of Normal and Pathological Homeostasis of the Immune System, INSERM U1163, Institut Imagine, and Université Paris Descartes-Sorbonne Paris Cité, Paris, France | en_US |
dc.description.affiliates | Department of Human Genetics, McGill University, Montreal, Quebec, Canada. | en_US |
dc.description.affiliates | Department of Pediatrics, McGill University, Montreal, Quebec, Canada. | en_US |
dc.description.affiliates | Research Institute, McGill University Health Centre, Montreal, Quebec, Canada. | en_US |
dc.type.contenttype | Text | en_US |
Appears in Collections: | Cancer Services |
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