Rare adult pilocytic astrocytoma of the septum pellucidum with novel RIN2::BRAF fusion

• Published in: Virchows Archiv : an international journal of pathology Vol. 482; no. 2; pp. 445 - 450
• Main Authors: Liu, Xinglei, Dai, Xiaoxiao, Dai, Chungang, Zhu, Qin, Chen, Ailin, Chen, Yanming, Chen, Nan, Chen, Ping, Rong, Rong, Shi, Changjun, Xiao, Sheng, Dong, Jun
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2023; Springer Nature B.V
• Subjects: Adolescent; Astrocytoma; Astrocytoma - genetics; Astrocytoma - pathology; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Brain tumors; Brief Report; Carrier Proteins; Cerebellum; Child; Dimerization; Genes; Glioblastoma; Glioma; Guanine Nucleotide Exchange Factors - metabolism; Humans; Hybridization; Kinases; Laboratories; Medicine; Medicine & Public Health; Neuraxis; Optic chiasm; Pathology; Pediatrics; Proteins; Proto-Oncogene Proteins B-raf - genetics; Septum; Septum Pellucidum - metabolism; Septum Pellucidum - pathology; Signal Transduction; Tumors; Young Adult; fusion; Adult pilocytic astrocytoma; Pellucid septum; RIN2::BRAF fusion
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-022-03477-3

Pilocytic astrocytoma is mostly a pediatric tumor with the majority of patients under age 20. Although tumors can occur throughout neuraxis, most tumors are in the cerebellum and optic chiasm. Pilocytic astrocytoma in unusual locations is often associated with different genetic alterations than the classic KIAA1549::BRAF fusion. We report a rare adult pilocytic astrocytoma of the septum pellucidum that presented with progressive headache. A detailed genomic evaluation found a fusion between BRAF and a novel partner RIN2 , a gene overexpressed in both low-grade glioma and glioblastoma. The RIN2::BRAF transcript encodes a chimeric protein containing a dimerization domain SH2 and an intact kinase domain, consistent with a prototypic oncogenic kinase rearrangement. In addition, we discuss the potential oncogenic mechanisms of BRAF signaling and its implication in targeted therapy with kinase inhibitors.