In:
Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii374-iii375
Kurzfassung:
Heterogeneous pathology in hemispheric low-grade gliomas (hemLGG) stress the importance of molecular testing in terms of prognosis prediction and targeted therapy options. METHODS Demographic data was collected and targeted genomic approach was employed in the single institutional study. RT-PCR was used to screen for KIAA1549-BRAF fusion and FGFR1 tyrosine-kinase domain duplication (FGFR1-ITD). Direct sequencing evaluated point mutations (BRAF ex15 and ex11, FGFR1 ex12 and ex14). Samples with no detected alteration were subjected to panel RNA-sequencing (FusionPlex Archer Diagnostics). RESULTS Within 2000–2019 were diagnosed 76 patients with hemLGG (median age 11.1y, range 0.0y–18.5y) comprising predominantly of ganglioglioma, dysembryoplastic neuroepithelial tumors, and diffuse astrocytoma. 40 % of hemLGG were characterized by BRAF alterations with over 2/3 of those cases harboring BRAF point mutations (two BRAFex11, 12 BRAFV600E). Notably, BRAF fusions were uncommon and detected only in six patients (two KIAA-BRAF fusion, two minor oncogenic BRAF variants, two non-KIAA BRAF fusion). 25 % of alterations were found in genes for receptor tyrosine kinases, consisting of seven patients with FGFR1-ITD, three FGFR2/3 fusions, two FGFR1 mutations, two ALK fusions, and one ROS fusion. Out of MAP kinase pathway, the most frequent alteration was IDH1 mutations (n=9). Two angiocentric gliomas were characterized by MYB-QKI fusion. CONCLUSION Targeted sequencing combined with RNA-sequencing is feasible to establish molecular diagnosis in majority of cases and reveal new and rare alterations. Significant prevalence of non-BRAF alterations explains heterogeneity among hemLGG.
Materialart:
Online-Ressource
ISSN:
1522-8517
,
1523-5866
DOI:
10.1093/neuonc/noaa222.424
Sprache:
Englisch
Verlag:
Oxford University Press (OUP)
Publikationsdatum:
2020
ZDB Id:
2094060-9
