Novel activating BRAF fusion identifies a recurrent alternative mechanism for ERK activation in pediatric Langerhans cell histiocytosis Journal Article
| Authors: | Zarnegar, S.; Durham, B. H.; Khattar, P.; Shukla, N. N.; Benayed, R.; Lacouture, M. E.; Lavi, E.; Lyden, D. C.; Diamond, E. L.; Dunkel, I. J.; Abdel-Wahab, O. |
| Article Title: | Novel activating BRAF fusion identifies a recurrent alternative mechanism for ERK activation in pediatric Langerhans cell histiocytosis |
| Abstract: | Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterized by constitutive activation of extracellular signal-regulated kinase (ERK). Genomic characterization has identified activating point mutations including mutually exclusive BRAFV600E and activating MAP2K1 mutations to be responsible for ERK activation in a majority of pediatric LCH patients. Here, we report the discovery of a novel BRAF kinase fusion, PACSIN2-BRAF, in a child with multisystem LCH. This is the second reported case of an activating BRAF kinase fusion and indicates a recurrent pathologic mechanism. Genomic evaluation for activating kinase fusions should be strongly considered in pediatric LCH patients lacking more common mutations. © 2017 Wiley Periodicals, Inc. |
| Keywords: | immunohistochemistry; mitogen activated protein kinase; child; clinical article; controlled study; human tissue; preschool child; unclassified drug; oncoprotein; gene mutation; human cell; promoter region; genetics; prednisone; clinical trial; case report; pathophysiology; genetic analysis; mitogen activated protein kinase kinase 1; skin defect; protein; enzyme activation; in vitro study; mutational analysis; vinblastine; bone lesion; oncogene proteins, fusion; mitogen activated protein kinase 1; adaptor proteins, signal transducing; extracellular signal-regulated map kinases; point mutation; epidermal growth factor receptor 3; signal transducing adaptor protein; b raf kinase; braf; genomic dna; proto-oncogene proteins b-raf; braf protein, human; langerhans cell histiocytosis; myeloid neoplasia; vemurafenib; histiocytosis, langerhans-cell; dabrafenib; trametinib; t6 antigen; humans; human; male; priority journal; article; kinase fusion; cobimetinib; lch; pacsin2; pacsin2 protein; pacsin2 protein, human |
| Journal Title: | Pediatric Blood and Cancer |
| Volume: | 65 |
| Issue: | 1 |
| ISSN: | 1545-5009 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2018-01-01 |
| Start Page: | e26699 |
| Language: | English |
| DOI: | 10.1002/pbc.26699 |
| PUBMED: | 28748614 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 January 2018 -- Source: Scopus |
