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Ref Type
PMID (29872711)
Authors Linzey JR, Marini B, McFadden K, Lorenzana A, Mody R, Robertson PL, Koschmann C
Title Identification and targeting of an FGFR fusion in a pediatric thalamic "central oligodendroglioma".
Journal NPJ precision oncology
Vol 1
Issue 1
Date 2017
Abstract Text Approximately 1-5% of pediatric intracranial tumors originate in the thalamus. While great strides have been made to identify consistent molecular markers in adult oligodendrogliomas, such as the 1p/19q co-deletion, it is widely recognized that pediatric oligodendrogliomas have a vastly different molecular make-up. While pediatric thalamic or "central oligodendrogliomas" are histologically similar to peripheral pediatric oligodendrogliomas, they are behaviorally distinct and likely represent a cohesive, but entirely different entity. We describe a case of a 10-year-old girl who was diagnosed with an anaplastic glioma with features consistent with the aggressive entity often diagnosed as central or thalamic oligodendroglioma. We performed whole-exome (paired tumor and germline DNA) and transcriptome (tumor RNA) sequencing, which demonstrated an FGFR3-PHGDH fusion. We describe this fusion and our rationale for pursuing personalized, targeted therapy for the patient's tumor that may potentially play a role in the treatment of similar cases.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
FGFR3 PHGDH FGFR3 - PHGDH fusion unknown FGFR3-PHGDH results from the fusion of FGFR3 and PHGDH (PMID: 29872711). FGFR3-PHGDH has been identified in thalamic oligodendrogliomas (PMID: 29872711, PMID: 32832832), but has not been biochemically characterized and therefore, the effect on protein function is unknown (PubMed, Jul 2022).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR3 - PHGDH childhood oligodendroglioma predicted - sensitive Ponatinib Case Reports/Case Series Actionable In a clinical case study, a pediatric thalamic oligodendroglioma patient who achieved a partial response when treated with radiation therapy, was found to harbor an FGFR3-PHGDH fusion, and subsequent Iclusig (ponatinib) treatment led to a tumor reduction of 15% (compared to post-radiation scans), and an ongoing partial response lasting seven moths post-treatment initiation (PMID: 29872711). 29872711