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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.

SUBMITTER: Zarnegar S

PROVIDER: S-EPMC6053915 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Novel activating BRAF fusion identifies a recurrent alternative mechanism for ERK activation in pediatric Langerhans cell histiocytosis.

Zarnegar Sara S Durham Benjamin H BH Khattar Pallavi P Shukla Neerav N NN Benayed Ryma R Lacouture Mario E ME Lavi Ehud E Lyden David C DC Diamond Eli L EL Dunkel Ira J IJ Abdel-Wahab Omar O

Pediatric blood & cancer 20170727 1

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 sec ...[more]

PMID: 28748614

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