The importance of escalating molecular diagnostics in patients with low-grade pediatric brain cancer.

TitleThe importance of escalating molecular diagnostics in patients with low-grade pediatric brain cancer.
Publication TypeJournal Article
Year of Publication2023
AuthorsAssaad MAl, Gundem G, Liechty B, Sboner A, Medina J, Papaemmanuil E, Sternberg CN, Marks A, Souweidane MM, Greenfield JP, Tran I, Snuderl M, Elemento O, Imielinski M, Pisapia DJ, Mosquera JMiguel
JournalCold Spring Harb Mol Case Stud
Date Published2023 Dec
KeywordsAstrocytoma, Brain Neoplasms, Child, Humans, Male, Mutation, Pathology, Molecular, Proto-Oncogene Proteins B-raf

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for BRAF rearrangement but harboring a BRAF p.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-yr-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing. Whole-genome and RNA-seq analysis identified an internal tandem duplication in FGFR1 and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes.

Alternate JournalCold Spring Harb Mol Case Stud
PubMed ID37652664
PubMed Central IDPMC10815291
Grant ListUL1 TR001863 / TR / NCATS NIH HHS / United States
Related Faculty: 
David Pisapia, M.D. Juan Miguel Mosquera, M.D. Benjamin L. Liechty, M.D. Andrea Sboner, Ph.D.

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