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Table of Contents
Year : 2019  |  Volume : 2  |  Issue : 2  |  Page : 141-142

Does BRAF V600E mutation change the treatment in craniopharyngioma?

Department of Radiation Oncology, Kayseri Education and Research Hospital, Kayseri, Turkey

Date of Web Publication10-Jan-2020

Correspondence Address:
Dr. Yasemin Benderli Cihan
Department of Radiation Oncology, Kayseri Education and Research Hospital, 38010 Kayseri
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJNO.IJNO_11_19

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How to cite this article:
Cihan YB. Does BRAF V600E mutation change the treatment in craniopharyngioma?. Int J Neurooncol 2019;2:141-2

How to cite this URL:
Cihan YB. Does BRAF V600E mutation change the treatment in craniopharyngioma?. Int J Neurooncol [serial online] 2019 [cited 2022 Jun 27];2:141-2. Available from: https://www.Internationaljneurooncology.com/text.asp?2019/2/2/141/275529


Craniopharyngiomas (CGs) are rare, benign, epithelial tumors located in the sellar/suprasellar region originating from the epithelial residues of the Rathke sac. They constitute 2%–5% of all intracranial tumors and 6%–13% of childhood tumors. Although they can be seen at any age, they show epidemiological bimodal age distribution. The first peak is between the ages of 5 and 14, and the second peak is between the ages of 50 and 74. They become a fairly large mass before becoming symptomatic due to their slow growth. They usually present with endocrine dysfunctions and visual disturbances. Headache is the most common complaint in CGs' clinic.[1],[2],[3] Pathologically, there are two subtypes, adamantinomatous and solid papillary. Papillary CG is generally seen in adults, but it is seen in pediatric age group. CGs are pathologically heterogeneous as well as radiologically they do not constitute a standard view. They can be completely cystic, completely solid, or both cystic and solid. Computed tomography, magnetic resonance imaging, and cerebral angiography are the main investigations. The treatment is planned according to the patient with a multidisciplinary approach. Treatment modalities include surgery, chemotherapy, and radiotherapy. Surgical gold is the standard treatment in CGs, and the aim is to perform a total gross resection with minimal morbidity. In the case of large-volume tumors, small age, and recurrent hydrocephalus, relapse is more common, whereas total resection and recurrence after subtotal resection are less frequent in radiotherapy. Despite total excision of the tumor, recurrence ranges between 5% and 30%. However, when the literature is examined, it is seen that there is no growth in residual tumors or the tumor recurred after total removal of tumor. The cause of recurrence and the recurrence of which tumor is not strictly determined. The most common cause is the total absence of tumor. In case of relapse, surgical treatment and/or radiotherapy is applied.[1],[2],[3],[4]

Today, the most common somatic mutations in CG oncogenesis are BRAF and CTNNB1. The BRAF gene is a member of the RAF gene family encoding the serine-threonine kinase protein located on chromosome 7q23. The BR600 gene on the 7th chromosome, which encodes the BRAF protein, is located on the 15th exon through the V600E mutation with the replacement of glutamic acid with valine. BRAF with V600E mutation shows structural activation, activates the MAPK pathway without any signal, and stimulates tumorigenesis.[1],[2],[3] In some studies, it was reported that the frequency of BRAF V600E mutation in CGs is around 76%–96%.[1],[2] Brastianos et al. investigated the distribution of BRAF mutations among the subvariants of CGs. The BRAF mutation was 100% in adamantinomatous variant and 95% in papillary variant cases.[2] In a review presented by Prieto and Pascual, a 90% BRAF mutation was seen in papillary-type CGs.[5] In most of the studies, there is a relationship between BRAF mutation and aggressive findings and recurrence. In a study by La Corte et al. on the papillary type of CGs, BRAF V600E reported that the mutation was usually seen in adults, but not calcified and suprasellar.[3] In literature, the recurrence of the tumor was thought to be related to the BRAF V600E mutation. BRAF-V600E mutation, which promotes cell growth by constitutively activating the MEK/ERK pathway. It was thought that inhibition of BRAF pathway could prevent recurrence and BRAF or MEK inhibitors were started to be used. BRAF and BRAF/MEK inhibitor has been shown to be effective by targeting recurrent CPs in two clinical case reports worldwide.[4],[6] In literature, studies on CG in which BRAF and MEK inhibitors were tested are case based, and clinical study is not currently available. Its role in neoadjuvant therapy with its efficacy in recurrence had begun to be explored. The role of BRAF inhibitors in neoadjuvant therapy in the treatment of BRAF mutant CG is investigated in a recent clinical study (Alliance A071601).[7] Rostami et al. reported that BRAF V600E mutation had recurrent papillary CG cases with BRAF inhibitor dabrafenib and MEK inhibitor trametinib, resulting in a 91% reduction in the tumor.[8] It was reported that panhypopituitarism and neurological symptoms improved and tumor shrinkage was achieved with BRAF inhibitor in a patient with unresectable and radiotherapy resistant CG.[9]

In conclusion, screening of BRAF V600E mutations in CG cases seems to play an important role in the prevention of recurrence of the disease and determination of possible treatment strategies. BRAF inhibitors can take their place in the CG treatment algorithm in the coming years. Long-term follow-up studies with more patients are needed to understand its place in treatment.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Chen X, Tong Y, Shi Z, Chen H, Yang Z, Wang Y, et al. Noninvasive molecular diagnosis of craniopharyngioma with MRI-based radiomics approach. BMC Neurol 2019;19:6.  Back to cited text no. 1
Brastianos PK, Taylor-Weiner A, Manley PE, Jones RT, Dias-Santagata D, Thorner AR, et al. Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet 2014;46:161-5.  Back to cited text no. 2
La Corte E, Younus I, Pivari F, Selimi A, Ottenhausen M, Forbes JA, et al. BRAF V600E mutant papillary craniopharyngiomas: A single-institutional case series. Pituitary 2018;21:571-83.  Back to cited text no. 3
Borrill R, Cheesman E, Stivaros S, Kamaly-Asl ID, Gnanalingham K, Kilday JP. Papillary craniopharyngioma in a 4-year-old girl with BRAF V600E mutation: A case report and review of the literature. Childs Nerv Syst 2019;35:169-73.  Back to cited text no. 4
Prieto R, Pascual JM. Can tissue biomarkers reliably predict the biological behavior of craniopharyngiomas? A comprehensive overview. Pituitary 2018;21:431-42.  Back to cited text no. 5
Himes BT, Ruff MW, Van Gompel JJ, Park SS, Galanis E, Kaufmann TJ, et al. Recurrent papillary craniopharyngioma with BRAF V600E mutation treated with dabrafenib: Case report. J Neurosurg 2018;1:1-5.  Back to cited text no. 6
Fujio S, Juratli TA, Arita K, Hirano H, Nagano Y, Takajo T, et al. A clinical rule for preoperative prediction of BRAF mutation status in craniopharyngiomas. Neurosurgery 2019;85:204-10.  Back to cited text no. 7
Rostami E, Witt Nyström P, Libard S, Wikström J, Casar-Borota O, Gudjonsson O, et al. Recurrent papillary craniopharyngioma with BRAFV600E mutation treated with neoadjuvant-targeted therapy. Acta Neurochir (Wien) 2017;159:2217-21.  Back to cited text no. 8
Roque A, Odia Y. BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors. CNS Oncol 2017;6:95-9.  Back to cited text no. 9


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