title: Oncogenic KIAA1549-BRAF fusion with activation of the MAPK/ERK pathway in pediatric oligodendrogliomas.
abstract: Pediatric oligodendrogliomas (pODGs) are rare central nervous system tumors, and comparatively little is known about their molecular pathogenesis. Co-deletion of 1p/19q; and IDH1, CIC, and FUBP1 mutations, which are molecular signatures of adult oligodendrogliomas, are extremely rare in pODGs. In this report, two pODGs, one each of grade II and grade III, were evaluated using clinical, radiological, histopathologic, and follow-up methods. IDH1, TP53, CIC, H3F3A, and BRAF-V600 E mutations were analyzed by Sanger sequencing and immunohistochemical methods, and 1p/19q co-deletion was analyzed by fluorescence in situ hybridization. PDGFRA amplification, BRAF gain, intragenic duplication of FGFR-TKD, and KIAA1549-BRAF fusion (validated by Sanger sequencing) were analyzed by real-time reverse transcription PCR. Notably, both cases showed the oncogenic KIAA1549_Ex15-BRAF_Ex9 fusion transcript. Further, immunohistochemical analysis showed activation of the MAPK/ERK pathway in both of these cases. However, neither 1p/19q co-deletion; IDH1, TP53, CIC, H3F3A, nor BRAF-V600 E mutation; PDGFRA amplification; BRAF gain; nor duplication of FGFR-TKD was identified. Overall, this study highlights that pODGs can harbor the KIAA1549-BRAF fusion with aberrant MAPK/ERK signaling, and there exists an option of targeting these pathways in such patients. These results indicate that pODGs with the KIAA1549-BRAF fusion may represent a subset of this rare tumor that shares molecular and genetic features of pilocytic astrocytomas. These findings will increase our understanding of pODGs and may have clinical implications.
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India; Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.
authors: Anupam
authors: A
authors: Kumar
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors: Pankaj
authors: P
authors: Pathak
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors: Suvendu
authors: S
authors: Purkait
authors: Genomics and Molecular Medicine, Council of Scientific and Industrial Research - Institute of Genomics and Integrative Biology, New Delhi, India.
authors: Mohammed
authors: M
authors: Faruq
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors: Prerana
authors: P
authors: Jha
authors: Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India.
authors: Supriya
authors: S
authors: Mallick
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors: Vaishali
authors: V
authors: Suri
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors: Mehar C
authors: MC
authors: Sharma
authors: Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.
authors: Ashish
authors: A
authors: Suri
authors: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India. Electronic address: sarkar.chitra@gmail.com.
authors: Chitra
authors: C
authors: Sarkar
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D009837:Oligodendroglioma / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics
chemical_list: D015514:Oncogene Proteins, Fusion; D020796:Receptor, Platelet-Derived Growth Factor alpha; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: BRAF; KIAA1549; MAPK/ERK; pediatric oligodendroglioma