Novel activating BRAF fusion identifies a recurrent alternative mechanism for ERK activation in pediatric Langerhans cell histiocytosis. Issue 1 (27th July 2017)

• Record Type: Journal Article
• Authors: Zarnegar, Sara; Durham, Benjamin H.; Khattar, Pallavi; Shukla, Neerav N.; Benayed, Ryma; Lacouture, Mario E.; Lavi, Ehud; Lyden, David C.; Diamond, Eli L.; Dunkel, Ira J.; Abdel‐Wahab, Omar
• Is Part Of: Pediatric blood & cancer. Volume 65:Issue 1(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-07-27
• Subjects: BRAF -- kinase fusion -- Langerhans cell histiocytosis -- LCH -- myeloid neoplasia -- PACSIN2; Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.26699
• Languages: English
• ISSNs: 1545-5009

Abstract

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 BRAF V600E 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.