Rapid fully-automated assay for routine molecular diagnosis of <i>BRAF</i> mutations for personalized therapy of low grade gliomas

Merlin, Marie-Sophie; Gilson, Pauline; Rouyer, Marie; Chastagner, Pascal; Doz, François; Varlet, Pascale; Leroux, Agnès; Gauchotte, Guillaume; Merlin, Jean‐Louis

doi:10.1080/08880018.2019.1679304

Cited by 4 publications

(2 citation statements)

References 35 publications

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“…Histologically, the GFAP stain highlighted the glial components, whereas positive staining for synaptophysin, CgA and NeuN labeled the neuronal/ganglion cell components in the GGs ( 30 ). In addition, the immunohistochemistry of BRAF V600E, a common molecular feature of GGs, could be helpful ( 31 , 32 ). The previously reported case had no detailed description of histological performance.…”

Section: Discussionmentioning

confidence: 99%

Anaplastic ganglioglioma originating from the medulla oblongata: case report

Han¹,

Guan²,

Song³

2021

Transl Cancer Res TCR

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Ganglioglioma (GG) is a rare kind of intracranial tumor with low potential malignancy (WHO grade I), which could occur in any part of the brain. However, a patient with anaplastic ganglioglioma (WHO grade III) in the medulla oblongata is a more peculiar and rare clinical case. In our report, we presented a case of a 45-year-old man with anaplastic ganglioglioma (WHO grade III) in the medulla oblongata, who was perplexed with dysphagia, choking and left-sided numbness for two and a half years. The head magnetic resonance imaging (MRI) showed a 2.7 cm × 2.6 cm lesion in the medulla oblongata with slightly low signal on T1 weighted image (T1WI) and heterogeneous high signal without calcifications on T2 weighted image (T2WI). The Physical Examination manifested that the patient showed a chronic appearance, along with the damage of oculomotor nerve, glossopharyngeal and vagus nerves and spinal thalamus lateral tract and rope body. Subsequently, the patient underwent surgical and common radiotherapy treatment, which might delay the tumor recurrence and contribute to a better overall survival. Unexpectedly, tentative chemotherapy was carried out when the tumor showed the recurrence trend and anaplastic feature. Our presentation of this case would emphasize the rarity and significance of the diagnosis, differentiation and treatment of such tumors, demanding more clinical cases for exploration.

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Section: Discussionmentioning

confidence: 99%

Anaplastic ganglioglioma originating from the medulla oblongata: case report

Han¹,

Guan²,

Song³

2021

Transl Cancer Res TCR

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“…However, using a digital droplet PCR, the BRAF-KIAA1549 fusion was detected from a minimal amount of FFPE tissue samples (one nanogram of DNA extracted) in pilocytic astrocytoma with a sensitivity and specificity of 100% compared with RNA sequencing [45]. Most recently, the BRAF V600E mutation in the FFPE samples of paediatric and adult LGGs were detected using a fully automated PCR with 100% sensitivity and specificity when compared with PCR and next-generation sequencing [46]. The application of liquid biopsies (blood, serum and cerebrospinal fluid (CSF)) has successfully bridged the gap between glioma patients and diagnosis with the identification of circulating tumour DNA [47,48].…”

Section: Braf Mutations As Biomarkers In Paediatric Low-grade Gliomasmentioning

confidence: 99%

Paediatric Gliomas: BRAF and Histone H3 as Biomarkers, Therapy and Perspective of Liquid Biopsies

Tan

Wijesinghe

Kamarudin

et al. 2021

Cancers

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Paediatric gliomas categorised as low- or high-grade vary markedly from their adult counterparts, and denoted as the second most prevalent childhood cancers after leukaemia. As compared to adult gliomas, the studies of diagnostic and prognostic biomarkers, as well as the development of therapy in paediatric gliomas, are still in their infancy. A body of evidence demonstrates that B-Raf Proto-Oncogene or V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) and histone H3 mutations are valuable biomarkers for paediatric low-grade gliomas (pLGGs) and high-grade gliomas (pHGGs). Various diagnostic methods involving fluorescence in situ hybridisation, whole-genomic sequencing, PCR, next-generation sequencing and NanoString are currently used for detecting BRAF and histone H3 mutations. Additionally, liquid biopsies are gaining popularity as an alternative to tumour materials in detecting these biomarkers, but still, they cannot fully replace solid biopsies due to several limitations. Although histone H3 mutations are reliable prognosis biomarkers in pHGGs, children with these mutations have a dismal prognosis. Conversely, the role of BRAF alterations as prognostic biomarkers in pLGGs is still in doubt due to contradictory findings. The BRAF V600E mutation is seen in the majority of pLGGs (as seen in pleomorphic xanthoastrocytoma and gangliomas). By contrast, the H3K27M mutation is found in the majority of paediatric diffuse intrinsic pontine glioma and other midline gliomas in pHGGs. pLGG patients with a BRAF V600E mutation often have a lower progression-free survival rate in comparison to wild-type pLGGs when treated with conventional therapies. BRAF inhibitors (Dabrafenib and Vemurafenib), however, show higher overall survival and tumour response in BRAF V600E mutated pLGGs than conventional therapies in some studies. To date, targeted therapy and precision medicine are promising avenues for paediatric gliomas with BRAF V600E and diffuse intrinsic pontine glioma with the H3K27M mutations. Given these shortcomings in the current treatments of paediatric gliomas, there is a dire need for novel therapies that yield a better therapeutic response. The present review discusses the diagnostic tools and the perspective of liquid biopsies in the detection of BRAF V600E and H3K27M mutations. An in-depth understanding of these biomarkers and the therapeutics associated with the respective challenges will bridge the gap between paediatric glioma patients and the development of effective therapies.

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