Dataset Information

Management of Inoperable Supra-Sellar Low-Grade Glioma With BRAF Mutation in Young Children.

ABSTRACT: Pediatric low-grade gliomas (PLGGs) are the most common central nervous system (CNS) tumors in children. The current standard of care for surgically unresectable and/or progressive cases of PLGGs includes combination chemotherapy. PLGGs are molecularly characterized by alterations in the RAS/RAF/MAPK/ERK pathway in a majority of tumors. PLGGs harboring the BRAF-V600E mutation respond poorly to current chemotherapy strategies. We present a case of a two-year-old female with biopsy-proven low-grade glioma (LGG, pilocytic astrocytoma) involving the hypothalamic/optic chiasm region. At presentation, she had obstructive hydrocephalus, bitemporal hemianopia, central hypothyroidism, and right-sided hemiparesis due to the location/mass effect of the tumor. She was initially treated with chemotherapy (vincristine/carboplatin), but her tumor progressed at six weeks of treatment. She was subsequently started on dabrafenib as her tumor was positive for BRAF-V600E mutation. Dabrafenib monotherapy resulted in dramatic improvement in her clinical symptoms and near-complete resolution of tumor. Our experience and review of the literature suggest that LGGs with BRAF-V600E mutations may benefit from upfront targeted therapy in children. There is an urgent need for prospective clinical trials comparing the efficacy of upfront BRAF inhibitors versus standard chemotherapy in PLGGs with BRAF mutations.

SUBMITTER: Howden K

PROVIDER: S-EPMC8656291 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Management of Inoperable Supra-Sellar Low-Grade Glioma With BRAF Mutation in Young Children.

Howden Kaitlyn K Chapman Stacy S Serletis Demitre D Kazina Colin C Rafay Mubeen F MF Faury Damien D Hazrati Lili-Naz LN Jabado Nada N Vanan Magimairajan Issai MI

Cureus 20211109 11

Pediatric low-grade gliomas (PLGGs) are the most common central nervous system (CNS) tumors in children. The current standard of care for surgically unresectable and/or progressive cases of PLGGs includes combination chemotherapy. PLGGs are molecularly characterized by alterations in the RAS/RAF/MAPK/ERK pathway in a majority of tumors. PLGGs harboring the BRAF-V600E mutation respond poorly to current chemotherapy strategies. We present a case of a two-year-old female with biopsy-proven low-grad ...[more]

PMID: 34926002

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Project description:Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed.

Dataset Information

Management of Inoperable Supra-Sellar Low-Grade Glioma With BRAF Mutation in Young Children.

Publications

Management of Inoperable Supra-Sellar Low-Grade Glioma With BRAF Mutation in Young Children.

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