Journal article
Dual activating FGFR1 mutations in pediatric pilomyxoid astrocytoma
Molecular genetics & genomic medicine, v 9(2), 1597
Feb 2021
PMID: 33448156
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Pilomyxoid astrocytomas are an aggressive subtype of astrocytoma, not graded by WHO, frequently located in hypothalamic/chiasmatic region, affecting diencephalic structures, and characterized by shorter survival and high recurrence rates. Pilomyxoid astrocytoma management remains controversial, with pathologic tissue diagnosis and relief of mass effect being the main goals of surgery while avoiding treatment-related morbidity, including vision loss, panhypopituitarism, and hypothalamic dysfunction. Chemotherapy (typically vincristine and carboplatin) in all pediatric patients and radiation therapy in pediatric patients over 5 years of age are used for treatment.
Methods: We report clinical presentation, surgical management, and whole exome sequencing results in a pediatric patient with the subtotally resected pilomyxoid astrocytoma.
Results: We identified two somatic activating missense mutations affecting FGFR1, including FGFR1 p.K656E and FGFR1 p.V561M. While the former is a known hotspot mutation that is both activating and transforming, the latter has been described as a gatekeeper mutation imparting resistance to FGFR inhibitors. Interestingly, both mutations were present with similar variant allele frequency within the tumor.
Conclusion: Similar variant allele frequencies of FGFR1 p.K656E and FGFR1 p.V561M mutations in our patient's tumor suggest that these mutations may have occurred at similar time points. Use of FGFR inhibitors in addition to STAT3 or PI3K/mTOR inhibition may prove a useful strategy in targeting our patient's pilomyxoid astrocytoma.
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Details
- Title
- Dual activating FGFR1 mutations in pediatric pilomyxoid astrocytoma
- Creators
- Elena I. Fomchenko - Yale UniversityBenjamin C. Reeves - Yale UniversityWilliam Sullivan - Yale UniversityAsher M. Marks - Yale UniversityAnita Huttner - Yale UniversityKristopher T. Kahle - Yale UniversityE. Zeynep Erson-Omay - Yale University
- Publication Details
- Molecular genetics & genomic medicine, v 9(2), 1597
- Publisher
- Wiley
- Number of pages
- 8
- Grant note
- National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) National Human Genome Research Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) UM1HG006504-05 / NIHM
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurology
- Web of Science ID
- WOS:000607526800001
- Scopus ID
- 2-s2.0-85099372284
- Other Identifier
- 991022004877504721
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- Web of Science research areas
- Genetics & Heredity