Genome sequencing identifies somatic BRAF duplication c.1794_1796dupTAC;p.Thr599dup in pediatric patient with low-grade ganglioglioma.

Finlay JL, Mardis ER, Koboldt DC, Ross N, Magrini V, Miller KE, Varga E, Boue DR, Cottrell CE, Leonard J, Fitch J, Coven SL, White P, Kelly B, Avenarius MR, Wilson RK, Gastier-Foster JM
Cold Spring Harb Mol Case Stud in press 02/06/2018


Gangliogliomas [WHO grade I] are rare tumors affecting the central nervous system and are most frequently observed in children. Genome sequencing of tumors is being utilized at an increasing rate in both research and clinical settings to characterize the genetic factors that drive tumorigenesis. Here, we report a rare BRAF somatic mutation (NM_004333.4:c.1794_1796dupTAC; p.Thr599dup) in the tumor genome from a pediatric patient in her late teens, who was initially diagnosed with low-grade ganglioglioma at age 13. This duplication of three nucleotides duplicates the threonine residue at amino acid 599 of the BRAF protein. Based on previous studies, this variant is likely to increase kinase activity, similar to the well-characterized BRAF p.Val600Glu (V600E) pathogenic variant. In addition, while the p.T599dup somatic mutation has been documented rarely in human cancers, the variant has not been previously reported in ganglioglioma. The identification of this variant presents an opportunity to consider targeted therapy (e.g., BRAF inhibitor) for this patient.

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