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DC Field | Value | Language |
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dc.citation.endPage | 165 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 154 | - |
dc.citation.title | CANCER DISCOVERY | - |
dc.citation.volume | 6 | - |
dc.contributor.author | Diamond, Eli L. | - |
dc.contributor.author | Durham, Benjamin H. | - |
dc.contributor.author | Haroche, Julien | - |
dc.contributor.author | Yao, Zhan | - |
dc.contributor.author | Ma, Jing | - |
dc.contributor.author | Parikh, Sameer A. | - |
dc.contributor.author | Wang, Zhaoming | - |
dc.contributor.author | Choi, John | - |
dc.contributor.author | Kim, Eunhee | - |
dc.contributor.author | Cohen-Aubart, Fleur | - |
dc.contributor.author | Lee, Stanley Chun-Wei | - |
dc.contributor.author | Gao, Yijun | - |
dc.contributor.author | Micol, Jean-Baptiste | - |
dc.contributor.author | Campbell, Patrick | - |
dc.contributor.author | Walsh, Michael P. | - |
dc.contributor.author | Sylvester, Brooke | - |
dc.contributor.author | Dolgalev, Igor | - |
dc.contributor.author | Aminova, Olga | - |
dc.contributor.author | Heguy, Adriana | - |
dc.contributor.author | Zappile, Paul | - |
dc.contributor.author | Nakitandwe, Joy | - |
dc.contributor.author | Ganzel, Chezi | - |
dc.contributor.author | Dalton, James D. | - |
dc.contributor.author | Ellison, David W. | - |
dc.contributor.author | Estrada-Veras, Juvianee | - |
dc.contributor.author | Lacouture, Mario | - |
dc.contributor.author | Gahl, William A. | - |
dc.contributor.author | Stephens, Philip J. | - |
dc.contributor.author | Miller, Vincent A. | - |
dc.contributor.author | Ross, Jeffrey S. | - |
dc.contributor.author | Ali, Siraj M. | - |
dc.contributor.author | Briggs, Samuel R. | - |
dc.contributor.author | Fasan, Omotayo | - |
dc.contributor.author | Block, Jared | - |
dc.contributor.author | Heritier, Sebastien | - |
dc.contributor.author | Donadieu, Jean | - |
dc.contributor.author | Solit, David B. | - |
dc.contributor.author | Hyman, David M. | - |
dc.contributor.author | Baselga, Jose | - |
dc.contributor.author | Janku, Filip | - |
dc.contributor.author | Taylor, Barry S. | - |
dc.contributor.author | Park, Christopher Y. | - |
dc.contributor.author | Amoura, Zahir | - |
dc.contributor.author | Dogan, Ahmet | - |
dc.contributor.author | Emile, Jean-Francois | - |
dc.contributor.author | Rosen, Neal | - |
dc.contributor.author | Gruber, Tanja A. | - |
dc.contributor.author | Abdel-Wahab, Omar | - |
dc.date.accessioned | 2023-12-22T00:09:15Z | - |
dc.date.available | 2023-12-22T00:09:15Z | - |
dc.date.created | 2016-08-02 | - |
dc.date.issued | 2016-02 | - |
dc.description.abstract | Histiocytic neoplasms are clonal, hematopoietic disorders characterized by an accumulation of abnormal, monocyte-derived dendritic cells or macrophages in Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (non-LCH), respectively. The discovery of BRAF(V600E) mutations in approximately 50% of these patients provided the first molecular therapeutic target in histiocytosis. However, recurrent driving mutations in the majority of patients with BRAF(V600E)-wild-type non-LCH are unknown, and recurrent cooperating mutations in non-MAP kinase pathways are undefined for the histiocytic neoplasms. Through combined whole-exome and transcriptome sequencing, we identified recurrent kinase fusions involving BRAF, ALK, and NTRK1, as well as recurrent, activating MAP2K1 and ARAF mutations in patients with BRAF(V600E)-wild-type non-LCH. In addition to MAP kinase pathway lesions, recurrently altered genes involving diverse cellular pathways were identified. Treatment of patients with MAP2K1- and ARAF-mutated non-LCH using MEK and RAF inhibitors, respectively, resulted in clinical efficacy, demonstrating the importance of detecting and targeting diverse kinase alterations in these disorders. SIGNIFICANCE: We provide the first description of kinase fusions in systemic histiocytic neoplasms and activating ARAF and MAP2K1 mutations in non-Langerhans histiocytic neoplasms. Refractory patients with MAP2K1- and ARAF-mutant histiocytoses had clinical responses to MEK inhibition and sorafenib, respectively, highlighting the importance of comprehensive genomic analysis of these disorders. | - |
dc.identifier.bibliographicCitation | CANCER DISCOVERY, v.6, no.2, pp.154 - 165 | - |
dc.identifier.doi | 10.1158/2159-8290.CD-15-0913 | - |
dc.identifier.issn | 2159-8274 | - |
dc.identifier.scopusid | 2-s2.0-84957056573 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/20159 | - |
dc.identifier.url | http://cancerdiscovery.aacrjournals.org/content/6/2/154 | - |
dc.identifier.wosid | 000372323000024 | - |
dc.language | 영어 | - |
dc.publisher | AMER ASSOC CANCER RESEARCH | - |
dc.title | Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms | - |
dc.type | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | LANGERHANS CELL HISTIOCYTOSIS | - |
dc.subject.keywordPlus | ERDHEIM-CHESTER DISEASE | - |
dc.subject.keywordPlus | POSITIVE LUNG-CANCER | - |
dc.subject.keywordPlus | ORAL MEK INHIBITOR | - |
dc.subject.keywordPlus | CLONAL HEMATOPOIESIS | - |
dc.subject.keywordPlus | PHASE-II | - |
dc.subject.keywordPlus | EXPRESSION PROFILES | - |
dc.subject.keywordPlus | SOMATIC MUTATIONS | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | HIGH PREVALENCE | - |
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