Current concepts in ameloblastoma-targeted therapies in B-raf proto-oncogene serine/threonine kinase V600E mutation: Systematic review.

Content Provider	Europe PMC
Author	González-González, Rogelio López-Verdín, Sandra Lavalle-Carrasco, Jesús Molina-Frechero, Nelly Isiordia-Espinoza, Mario Carreón-Burciaga, Ramón G Bologna-Molina, Ronell
Copyright Year	2019
Abstract	BACKGROUNDAmeloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies. Different signaling pathways that participate in the progression of these tumors have been identified. B-raf proto-oncogene serine/threonine kinase (BRAF) is a protein involved in the behavior of ameloblastomas, and it is related to many cell mechanisms. BRAF gene mutations have been identified in ameloblastomas, of which the BRAF V600E (valine substituted by glutamic acid at amino acid 600) mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior. Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIMTo document the presence of BRAF V600E and additional mutations, their behavior, and targeted therapies in these tumors.METHODSAn electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, Cochrane, EMBASE, and SpringerLink using the terms “ameloblastomas”, “BRAF V600E”, “additional mutations”, and “targeted therapies”. Ameloblastomas were classified according to WHO guidelines. Inclusion criteria were articles in English, published not more than 10 years ago, and studies with laboratory works related to BRAF V600E. Articles were evaluated by two independent reviewers and retrieved for full-text evaluation. The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies. Descriptive statistical analysis was performed.RESULTSTwo independent reviewers, with a substantial concordance indicated by a kappa coefficient of k = 0.76, evaluated a total of 19 articles that were included in this study. The analysis registered 521 conventional ameloblastomas (AM), 81 unicystic ameloblastomas (UA), 13 ameloblastic carcinomas (AC), three metastatic ameloblastomas (MA), and six peripheral ameloblastomas (PA), of which the histopathological type, anatomic location, laboratory tests, expression of BRAF mutation, and additional mutations were registered. The BRAF V600E mutation was found in 297 AM (57%), 63 UA (77.7%), 3 AC (23%), 1 MA (50%), and 5 PA (83.3%). Follicular type predominated with a total of 116 cases (40%), followed by plexiform type with 63 cases (22.1%). Furthermore, both types presented additional mutations, in which alterations in JAK3 P132T, SMARCB1, PIK3CA, CTNNB1, SMO, and BRAF G606E genes were found. Four case reports were found with targeted therapy to BRAF V600E.CONCLUSIONThe identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.
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Journal	World Journal of Clinical Oncology [World J Clin Oncol]
Volume Number	11
DOI	10.5306/wjco.v11.i1.31
PubMed Central reference number	PMC6935689
Issue Number	1
PubMed reference number	31976308
e-ISSN	22184333
Language	English
Publisher	Baishideng Publishing Group Inc
Publisher Date	2020-01-01
Access Restriction	Open
Rights License	This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Subject Keyword	Ameloblastoma B-raf proto-oncogene serine/threonine kinase B-raf proto-oncogene serine/threonine kinase V600E Additional mutations Targeted therapies
Content Type	Text
Resource Type	Article
Subject	Oncology