mutation braf
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2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi16-vi16
Author(s):  
Erica Shen ◽  
Alireza Shams ◽  
Xianyuan Song ◽  
Ahmad Daher

Abstract Accounting for only 2% of all primary brain tumors, ganglioglioma is a rare neoplasm that most frequently arises in the temporal lobe in children or young adults. Ganglioglioma is the most common epilepsy-associated neoplasm and is typically composed of dysplastic ganglion cells and neoplastic glial cells. Recent publications have revealed that the activating p.V600E mutation in the BRAF oncogene is seen in 20-60% of gangliogliomas. However, the genetic landscape of ganglioglioma requires further elucidation, especially in gangliogliomas that arise from outside of the temporal lobe in adults. In this case series, we describe the genetic mutations of adult gangliogliomas originating outside of the temporal lobe in four patients aged 21 to 56 years. Targeted next generation sequencing via the MSK-IMPACT panel covering ~ 500 actionable mutations was used in all cases. None of the cases had the BRAF p.V600E mutation. Case 1 describes a left cerebellar cystic ganglioglioma with NTRK2 fusion mutation (NTRK2-DST) and a tumor mutation burden (TMB) = 0 mutation/megabase (mut/Mb). Case 2 describes a right parietal lobe cystic ganglioglioma with a BRAF-CLEC2Linversion mutation and TMB = 0 mut/Mb. Case 3 describes a cerebellar vermis ganglioglioma with a BRAF fusion mutation (BRAF-KIAA1549) and TMB = 0 mut/Mb. The last case describes a right cerebellopontine angle ganglioglioma with a MAP2K1 splicing mutation and TMB = 0.9 mut/Mb. To the best of our knowledge, the mutations identified in this case series have not been previously described in adult brain gangliogliomas. The BRAF-KIAA1549 fusion mutation has been found in spinal cord gangliogliomas, but not in brain gangliogliomas. MAP2K1 splicing mutations, unlike MAP2K1 in-frame deletions, have not been found in gangliogliomas. Finally, a different NTRK2 mutation (NTRK2-TLE4) has been described in a pediatric ganglioglioma, but NTRK2-DST has not been found in any adult gangliogliomas.


2021 ◽  
Vol 82 (5) ◽  
pp. 417
Author(s):  
S. Khamal ◽  
L. Echchad ◽  
M. Tounsi ◽  
H. Iraqi ◽  
M. Gharbi
Keyword(s):  

2021 ◽  
Vol 11 ◽  
Author(s):  
Elisa Grassi ◽  
Jody Corbelli ◽  
Giorgio Papiani ◽  
Maria Aurelia Barbera ◽  
Federica Gazzaneo ◽  
...  

Around 8–12% of patients with advanced colon rectal cancer (CRC) present with BRAF alterations, in particular V600E mutation, which is associated with right-side, poorly differentiated and mucinous type tumors. The presence of BRAF mutation (BRAF-mt) has been identified as a hallmark of poor prognosis and treatment optimization in this patient subgroup is an important goal. Currently, the standard of care is an aggressive strategy involving triplet chemotherapy and anti-VEGF agents, but new therapeutic approaches are emerging. Very promising results have been obtained with targeted therapy combinations, such as anti-BRAF agents plus anti-EGFR agents. Furthermore, around 60% of BRAF-mt patients show a strong association with high microsatellite instability (MSI-H) and immune checkpoint inhibitors could represent the new standard of care for this subgroup. The focus of this review is to summarize current strategies for BRAF-mt CRC treatment and highlight new therapeutic options.


2021 ◽  
Vol 42 ◽  
pp. A146
Author(s):  
T. Sobczak ◽  
E. Ribeiro ◽  
V. Guillotin ◽  
P. Duffau ◽  
P. Mercié ◽  
...  

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14021-e14021
Author(s):  
Deze Jia ◽  
Yi Lu ◽  
Xiaomin Li ◽  
Tiantian Han ◽  
Wanglong Deng ◽  
...  

e14021 Background: The updated 2016 edition of the WHO Classification of CNS tumors indicates that IDH1 R132H, H3 K27M mutations, and co-deletion of 1p19q are strong stratification and prognostic markers glioma. FISH/IHC, as the commonly detected methods, present specific false-negative rates in the actual condition. Methods: In our study, IDH1 R132H status of 158 cases was assessed by IHC and NGS, and H3 K27M statuses of 83 patients were evaluated by IHC and NGS. 22 positive cases of 1p/19q co-deletion, all confirmed by FISH, were assessed by NGS. Results: For IDH1 R132H, 2 cases were IHC negative and were positive as confirmed by NGS. Another 10 patients with weakly IHC positive results were negative in NGS. Combined with histologic hallmarks, 6 cases of these samples could be diagnosed as glioblastoma, IDH wildtype; 1 case with POLE could be diagnosed as giant cell glioblastoma; 3 cases with BRAF V600E mutation, BRAF fusion, and ATRX mutation, respectively, could be diagnosed as pilocytic astrocytoma. Towards H3 K27M, 3 cases with IHC weakly positive were negative in NGS. Among these samples, 2 cases were diagnosed as glioblastoma, IDH wildtype by molecular and histologic hallmarks, and 1 case was medulloblastoma, SHH. Using NGS, IDH1 R132H /H3 K27M statues can be distinctly distinguished in which that is unknown by IHC. The results of NGS and FISH showed a 90.9%(20/22) consistent rate for the 1p19q co-deletion. 1 case was 1p deletion and intact 19q by FISH while 1p19q co-deletion by NGS because of the 19p deletion. 1 case was 1p19q co-deletion by FISH but 1p19q wildtype by NGS, diagnosed as glioblastoma, IDH wildtype with chr7+/10-. Conclusions: In our study, the agreement between NGS results and clinical pathology diagnosis was approximately 100%. NGS may act as the primary technology of molecular classification in glioma in the future.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Angelica Gualtieri ◽  
Nikolina Kyprianou ◽  
Louise C. Gregory ◽  
Maria Lillina Vignola ◽  
James G. Nicholson ◽  
...  

AbstractGermline mutations in BRAF and other components of the MAPK pathway are associated with the congenital syndromes collectively known as RASopathies. Here, we report the association of Septo-Optic Dysplasia (SOD) including hypopituitarism and Cardio-Facio-Cutaneous (CFC) syndrome in patients harbouring mutations in BRAF. Phosphoproteomic analyses demonstrate that these genetic variants are gain-of-function mutations leading to activation of the MAPK pathway. Activation of the MAPK pathway by conditional expression of the BrafV600E/+ allele, or the knock-in BrafQ241R/+ allele (corresponding to the most frequent human CFC-causing mutation, BRAF p.Q257R), leads to abnormal cell lineage determination and terminal differentiation of hormone-producing cells, causing hypopituitarism. Expression of the BrafV600E/+ allele in embryonic pituitary progenitors leads to an increased expression of cell cycle inhibitors, cell growth arrest and apoptosis, but not tumour formation. Our findings show a critical role of BRAF in hypothalamo-pituitary-axis development both in mouse and human and implicate mutations found in RASopathies as a cause of endocrine deficiencies in humans.


2020 ◽  
Vol 176 ◽  
pp. S48
Author(s):  
Juliette Dufour ◽  
Bertrand Mathon ◽  
Mehdi Touat ◽  
Khê Hoang-Xuan ◽  
Mokhtari Karima ◽  
...  
Keyword(s):  

2020 ◽  
Vol 102 (2) ◽  
pp. e42-e44
Author(s):  
JDE Lee ◽  
C Gill ◽  
J Muzaffar ◽  
S Ahmed ◽  
R Amel-Kashipaz

Erdheim–Chester disease is a rare infiltrative histiocytic disorder with around 800 cases being reported worldwide. Patients most commonly present with skeletal pain, but the condition has been shown to affect multiple other organs. We describe a rare presentation in which the disease infiltrated the sinuses and affected an ex-RAF pilot’s vision. After extensive investigation of the elusive diagnosis, repeating of a molecular test using polymerase chain reaction analysis allowed for identification of a mutation (BRAF V600) ultimately leading to the diagnosis of Erdheim–Chester disease.


2020 ◽  
Vol 12 (1) ◽  
pp. 121-122
Author(s):  
R. Khemakhem ◽  
A. Chabrol ◽  
C. Givel ◽  
C. Tcherakian ◽  
E. Catherinot ◽  
...  
Keyword(s):  

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