| Title | Novel activating BRAF fusion identifies a recurrent alternative mechanism for ERK activation in pediatric Langerhans cell histiocytosis. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Zarnegar S, Durham BH, Khattar P, Shukla NN, Benayed R, Lacouture ME, Lavi E, Lyden DC, Diamond EL, Dunkel IJ, Abdel-Wahab O |
| Journal | Pediatr Blood Cancer |
| Volume | 65 |
| Issue | 1 |
| Date Published | 2018 Jan |
| ISSN | 1545-5017 |
| Keywords | Adaptor Proteins, Signal Transducing, Child, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Histiocytosis, Langerhans-Cell, Humans, Male, Oncogene Proteins, Fusion, Proto-Oncogene Proteins B-raf |
| 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. |
| DOI | 10.1002/pbc.26699 |
| Custom 1 | |
| Alternate Journal | Pediatr Blood Cancer |
| PubMed ID | 28748614 |
| PubMed Central ID | PMC6053915 |
| Grant List | K08 CA160647 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States R01 CA201247 / CA / NCI NIH HHS / United States R01 HL128239 / HL / NHLBI NIH HHS / United States |