Rare Cases of IDH1 Mutations in Spinal Cord Astrocytomas

N. A. Konovalov; D. S. Asyutin; E. G. Shayhaev; S. V. Kaprovoy; S. Yu. Timonin

doi:10.32607/actanaturae.10915

Rare Cases of IDH1 Mutations in Spinal Cord Astrocytomas

Acta Naturae ◽

10.32607/actanaturae.11155 ◽

2020 ◽

Vol 12 (2) ◽

pp. 70-73

Author(s):

N. A. Konovalov ◽

D. S. Asyutin ◽

E. G. Shayhaev ◽

S. V. Kaprovoy ◽

S. Yu. Timonin

Keyword(s):

Spinal Cord ◽

Brain Tumors ◽

Cns Tumors ◽

Occurrence Rate ◽

Intracranial Tumors ◽

Spinal Cord Tumors ◽

Astrocytoma Cells ◽

Idh1 Mutations ◽

Spinal Cord Astrocytoma

A low occurrence rate of spinal cord gliomas (4.3% of primary and glial CNS tumors) and the associated difficulties in building statistically significant cohorts of patients considerably slow down the development of effective approaches to the treatment of spinal cord tumors compared to brain tumors. Despite our extensiveknowledge regardingIDHmutations in intracranial tumors, mutations of this gene in spinal cord astrocytomas remain poorly understood. In thisstudy, we report on five cases of identified mutations in theIDH1gene in spinal cord astrocytoma cells, two of which are unique, as they have never been previously described in CNS gliomas.

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Contrast-Enhanced Ultrasound Assisted Surgery of Intramedullary Spinal Cord Tumors: Analysis of Technical Benefits and Intra-operative Microbubble Distribution Characteristics

Ultrasound in Medicine & Biology ◽

10.1016/j.ultrasmedbio.2020.10.017 ◽

2020 ◽

Author(s):

Ignazio G. Vetrano ◽

Antonio G. Gennari ◽

Alessandra Erbetta ◽

Francesco Acerbi ◽

Vittoria Nazzi ◽

...

Keyword(s):

Spinal Cord ◽

Distribution Characteristics ◽

Contrast Enhanced Ultrasound ◽

Spinal Cord Tumors ◽

Intramedullary Spinal Cord ◽

Contrast Enhanced ◽

Ultrasound Assisted

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The impact of intraoperative neurophysiological monitoring in spinal cord astrocytoma-surgery

Klinische Neurophysiologie ◽

10.1055/s-0030-1250974 ◽

2010 ◽

Vol 41 (01) ◽

Author(s):

S Grossauer ◽

V Tramontano ◽

L Bruckmann ◽

K Köck ◽

G Sqintani ◽

...

Keyword(s):

Spinal Cord ◽

Intraoperative Neurophysiological Monitoring ◽

Neurophysiological Monitoring ◽

The Impact ◽

Spinal Cord Astrocytoma

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ATYPICAL PRESENTATION OF SPINAL CORD TUMORS IN CHILDREN

Neuropediatrics ◽

10.1055/s-2006-945679 ◽

2006 ◽

Vol 37 (S 1) ◽

Author(s):

C Waisburg ◽

J Hukin ◽

F Durity ◽

E Roland ◽

A Hill

Keyword(s):

Spinal Cord ◽

Atypical Presentation ◽

Spinal Cord Tumors

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BIOM-62 SENSITIVE DETECTION AND DISCRIMINATION OF INTRACRANIAL TUMORS BY BLOOD

Neuro-Oncology ◽

10.1093/neuonc/noaa215.059 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii15-ii15

Author(s):

Farshad Nassiri ◽

Ankur Chakravarthy ◽

Shengrui Feng ◽

Roxana Shen ◽

Romina Nejad ◽

...

Keyword(s):

Dna Methylation ◽

Brain Tumors ◽

Model Performance ◽

High Sensitivity ◽

Circulating Tumor Dna ◽

Low Grade ◽

Learning Approaches ◽

Intracranial Tumors ◽

Cell Of Origin ◽

Tumor Dna

Abstract BACKGROUND The diagnosis of intracranial tumors relies on tissue specimens obtained by invasive surgery. Non-invasive diagnostic approaches, particularly for patients with brain tumours, provide an opportunity to avoid surgery and mitigate unnecessary risk to patients. We reasoned that DNA methylation profiles of circulating tumor DNA in blood can be used as a clinically useful biomarker for patients with brain tumors, given the specificity of DNA methylation profiles for cell-of-origin. METHODS We generated methylation profiles on the plasma of 608 patients with cancer (219 intracranial, 388 extracranial) and 60 healthy controls using a cell-free methylated DNA immunoprecipitation combined with deep sequencing (cfMeDIP-seq) approach. Using machine-learning approaches we generated and evaluated models to distinguish brain tumors from extracranial cancers that may metastasize to the brain, as well as additional models to discriminate common brain tumors included in the differential diagnosis of solitary extra-axial and intra-axial tumors. RESULTS We observed high sensitivity and discriminative capacity for our models to distinguish gliomas from other cancerous and healthy patients (AUC=0.99, 95%CI 0.96–1), with similar performance in IDH mutant and wildtype gliomas as well as in lower- and high-grade gliomas. Excluding non-malignant contributors to plasma methylation did not change model performance (AUC=0.982, 95%CI 0.93–1). Models generated to discriminate intracranial tumors from each other also demonstrated high accuracy for common extra-axial tumors (AUCmeningioma=0.89, 95%CI 0.80–0.97; AUChemangiopericytoma=0.95, 95%CI 0.73–1) as well as intra-axial tumors ranging from low-grade indolent glial-neuronal tumors (AUC 0.93, 95%CI 0.80 – 1) to diffuse intra-axial gliomas with distinct molecular composition (AUCIDH-mutant glioma = 0.82, 95%CI 0.66 -0.98; AUCIDH-wildtype-glioma = 0.71, 95%CI 0.53 – 0.9). Plasma cfMeDIP-seq signals originated from corresponding tumor tissue DNA methylation signals (r=0.37, p< 2.2e-16). CONCLUSIONS These results demonstrate the potential for cfMeDIP-seq profiles to not only detect circulating tumor DNA, but to accurately discriminate common intracranial tumors that share cell-of-origin lineages.

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Surgery of Spinal Cord Tumors Based on Anatomy

10.1007/978-981-15-7771-0 ◽

2021 ◽

Keyword(s):

Spinal Cord ◽

Spinal Cord Tumors

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EXTH-16. TREATMENT OF THREE DIFFERENT BRAF-V600E POSITIVE BRAIN TUMORS WITH VEMURAFENIB AND DABRAFENIB/TRAMETINIB: A CASE SERIES

Neuro-Oncology ◽

10.1093/neuonc/noaa215.370 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii90-ii90

Author(s):

Nikita Dhir ◽

Sheila Chandrahas ◽

Chibuzo O’Suoji ◽

Mohamad Al-Rahawan

Keyword(s):

Targeted Therapy ◽

Brain Tumors ◽

Tumor Regression ◽

Case Series ◽

Pediatric Brain Tumors ◽

Braf V600e ◽

Cns Tumors ◽

Braf Inhibitors ◽

Pediatric Brain ◽

Pediatric Cns Tumors

Abstract BACKGROUND The BRAF-V600E gene is a protein kinase involved in regulation of the mitogen activated protein kinase pathway (MAPK/MEK) and downstream extracellular receptor kinase (ERK). The BRAF-V600E mutation has a significant role in the progression of pediatric brain tumors. 85% of pediatric CNS tumors express the BRAF mutation. Thus, BRAF targeted therapy in pediatric CNS malignancies has potential to become the standard of care for tumors expressing this mutation. OBJECTIVE Current pediatric CNS brain tumor treatment focuses on chemotherapy and radiation, causing significant toxic side effects for patients. The significance of this case series lies in relaying our experience using targeted therapy in BRAF-V600E positive CNS pediatric brain tumors. METHODS We followed the disease course, progression, and treatment of three pediatric patients with three different CNS tumors. Each of these individuals was treated with surgical resection, chemotherapy, and/or radiation as per standard protocol. When that modality failed to reduce tumor progression, we found that each of their different tumors was BRAF-V600E positive and they were all started on targeted therapy. DISCUSSION Vemurafenib, Dabrafenib, and Trametinib are BRAF-V600E/MEK inhibitors that were initially used to treat melanomas. However, more research has shown that various pediatric CNS tumors are BRAF-V600 positive. Therapy with these BRAF inhibitors has been shown to slow tumor progression, but toxicity can be severe. This case series shows one patient with successful tumor regression, one patient with prolonged disease stabilization, and one patient with initial response but subsequent progression and ultimate death. It has been shown that using BRAF inhibitors in lower grade CNS tumors are more effective than higher grade CNS tumors. CONCLUSION The success of Vemurafenib and Dabrafenib/Trametinib in causing pediatric CNS tumor regression is promising, but further studies are needed to solidify their role in pediatric CNS cancers.

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