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Activating Non-V600 BRAF Mutation

MedGen UID:
1691876
•Concept ID:
C5205246
•
Cell or Molecular Dysfunction
Synonyms: Activating Non-Codon 600 BRAF Gene Mutation; Activating Non-Codon 600 BRAF Mutation; BRAF Class II Alteration; BRAF Class II Mutation; Class 2 BRAF Mutation; Class II BRAF Alteration; Class II BRAF Mutation; Non-Codon 600 Activating BRAF Gene Mutation; Non-Codon 600 Activating BRAF Mutation; Non-Codon 600 Activating BRAF1 Mutation; Non-Codon 600 B-RAF Activating Mutation; Non-Codon 600 B-RAF1 Activating Mutation; Non-Codon 600 BRAF Activating Mutation; Non-V600 Activating BRAF Mutation

Definition

A change in the nucleotide sequence of the BRAF gene that occurs outside of codon 600 and results in activation of both serine/threonine-protein kinase B-raf and its downstream signaling pathways. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVActivating Non-V600 BRAF Mutation

Professional guidelines

PubMed

Clinical characteristics and treatment outcomes of non-V600 E/K BRAF mutant melanoma patients: a single-institution experience.
Comito F, Aprile M, Pagani R, Siepe G, Sperandi F, Gruppioni E, Altimari A, De Biase D, Melotti B
Melanoma Res 2022 Dec 1;32(6):477-484. Epub 2022 Aug 29 doi: 10.1097/CMR.0000000000000854. PMID: 36039514
Melanoma with genetic alterations beyond the BRAFV600 mutation: management and new insights.
Awada G, Neyns B
Curr Opin Oncol 2022 Mar 1;34(2):115-122. doi: 10.1097/CCO.0000000000000817. PMID: 35050937
Applying Precision to the Management of BRAF-Mutant Metastatic Colorectal Cancer.
Johnson B, Kopetz S
Target Oncol 2020 Oct;15(5):567-577. doi: 10.1007/s11523-020-00747-5. PMID: 32889679Free PMC Article

Recent clinical studies

Etiology

Targeting Non-V600 Mutations in BRAF: A Single Institution Retrospective Analysis and Review of the Literature.
Chaudhary HA, Cannon TL, Winer A
Drugs R D 2024 Sep;24(3):395-403. Epub 2024 Aug 23 doi: 10.1007/s40268-024-00475-5. PMID: 39177935Free PMC Article
Clinical Activity of Mitogen-Activated Protein Kinase-Targeted Therapies in Patients With Non-V600 BRAF-Mutant Tumors.
Dankner M, Wang Y, Fazelzad R, Johnson B, Nebhan CA, Dagogo-Jack I, Myall NJ, Richtig G, Bracht JWP, Gerlinger M, Shinozaki E, Yoshino T, Kotani D, Fangusaro JR, Gautschi O, Mazieres J, Sosman JA, Kopetz S, Subbiah V, Davies MA, Groover AL, Sullivan RJ, Flaherty KT, Johnson DB, Benedetti A, Cescon DW, Spreafico A, Zogopoulos G, Rose AAN
JCO Precis Oncol 2022 Aug;6:e2200107. doi: 10.1200/PO.22.00107. PMID: 35977349Free PMC Article
Applying Precision to the Management of BRAF-Mutant Metastatic Colorectal Cancer.
Johnson B, Kopetz S
Target Oncol 2020 Oct;15(5):567-577. doi: 10.1007/s11523-020-00747-5. PMID: 32889679Free PMC Article
Targeted Therapy in Advanced Melanoma With Rare BRAF Mutations.
Menzer C, Menzies AM, Carlino MS, Reijers I, Groen EJ, Eigentler T, de Groot JWB, van der Veldt AAM, Johnson DB, Meiss F, Schlaak M, Schilling B, Westgeest HM, Gutzmer R, Pföhler C, Meier F, Zimmer L, Suijkerbuijk KPM, Haalck T, Thoms KM, Herbschleb K, Leichsenring J, Menzer A, Kopp-Schneider A, Long GV, Kefford R, Enk A, Blank CU, Hassel JC
J Clin Oncol 2019 Nov 20;37(33):3142-3151. Epub 2019 Oct 3 doi: 10.1200/JCO.19.00489. PMID: 31580757Free PMC Article
Response to Anti-EGFR Therapy in Patients with BRAF non-V600-Mutant Metastatic Colorectal Cancer.
Yaeger R, Kotani D, Mondaca S, Parikh AR, Bando H, Van Seventer EE, Taniguchi H, Zhao H, Thant CN, de Stanchina E, Rosen N, Corcoran RB, Yoshino T, Yao Z, Ebi H
Clin Cancer Res 2019 Dec 1;25(23):7089-7097. Epub 2019 Sep 12 doi: 10.1158/1078-0432.CCR-19-2004. PMID: 31515458Free PMC Article

Diagnosis

Hairy cell leukaemia with unusual BRAF mutations.
Maitre E, Macro M, Troussard X
J Cell Mol Med 2023 Sep;27(17):2626-2630. Epub 2023 Aug 2 doi: 10.1111/jcmm.17890. PMID: 37530550Free PMC Article
Non-V600E/K BRAF Mutations in Metastatic Melanoma: Molecular Description, Frequency, and Effectiveness of Targeted Therapy in a Large National Cohort.
Girod M, Dalle S, Mortier L, Dalac S, Leccia MT, Dutriaux C, Montaudié H, de Quatrebarbes J, Lesimple T, Brunet-Possenti F, Saiag P, Maubec E, Legoupil D, Stoebner PE, Arnault JP, Lefevre W, Lebbe C, Dereure O
JCO Precis Oncol 2022 Nov;6:e2200075. doi: 10.1200/PO.22.00075. PMID: 36356284
Clinical characteristics and treatment outcomes of non-V600 E/K BRAF mutant melanoma patients: a single-institution experience.
Comito F, Aprile M, Pagani R, Siepe G, Sperandi F, Gruppioni E, Altimari A, De Biase D, Melotti B
Melanoma Res 2022 Dec 1;32(6):477-484. Epub 2022 Aug 29 doi: 10.1097/CMR.0000000000000854. PMID: 36039514
Lung Cancer Driven by BRAF(G469V) Mutation Is Targetable by EGFR Kinase Inhibitors.
Huo KG, Notsuda H, Fang Z, Liu NF, Gebregiworgis T, Li Q, Pham NA, Li M, Liu N, Shepherd FA, Marshall CB, Ikura M, Moghal N, Tsao MS
J Thorac Oncol 2022 Feb;17(2):277-288. Epub 2021 Oct 12 doi: 10.1016/j.jtho.2021.09.008. PMID: 34648945
First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study.
Sullivan RJ, Infante JR, Janku F, Wong DJL, Sosman JA, Keedy V, Patel MR, Shapiro GI, Mier JW, Tolcher AW, Wang-Gillam A, Sznol M, Flaherty K, Buchbinder E, Carvajal RD, Varghese AM, Lacouture ME, Ribas A, Patel SP, DeCrescenzo GA, Emery CM, Groover AL, Saha S, Varterasian M, Welsch DJ, Hyman DM, Li BT
Cancer Discov 2018 Feb;8(2):184-195. Epub 2017 Dec 15 doi: 10.1158/2159-8290.CD-17-1119. PMID: 29247021

Therapy

A Next-Generation BRAF Inhibitor Overcomes Resistance to BRAF Inhibition in Patients with BRAF-Mutant Cancers Using Pharmacokinetics-Informed Dose Escalation.
Yaeger R, McKean MA, Haq R, Beck JT, Taylor MH, Cohen JE, Bowles DW, Gadgeel SM, Mihalcioiu C, Papadopoulos KP, Diamond EL, Sturtz KB, Feng G, Drescher SK, Reddy MB, Sengupta B, Maity AK, Brown SA, Singh A, Brown EN, Baer BR, Wong J, Mou TC, Wu WI, Kahn DR, Gadal S, Rosen N, Gaudino JJ, Lee PA, Hartley DP, Rothenberg SM
Cancer Discov 2024 Sep 4;14(9):1599-1611. doi: 10.1158/2159-8290.CD-24-0024. PMID: 38691346Free PMC Article
Molecular Pathways and Mechanisms of BRAF in Cancer Therapy.
Poulikakos PI, Sullivan RJ, Yaeger R
Clin Cancer Res 2022 Nov 1;28(21):4618-4628. doi: 10.1158/1078-0432.CCR-21-2138. PMID: 35486097Free PMC Article
Targeted Therapy in Advanced Melanoma With Rare BRAF Mutations.
Menzer C, Menzies AM, Carlino MS, Reijers I, Groen EJ, Eigentler T, de Groot JWB, van der Veldt AAM, Johnson DB, Meiss F, Schlaak M, Schilling B, Westgeest HM, Gutzmer R, Pföhler C, Meier F, Zimmer L, Suijkerbuijk KPM, Haalck T, Thoms KM, Herbschleb K, Leichsenring J, Menzer A, Kopp-Schneider A, Long GV, Kefford R, Enk A, Blank CU, Hassel JC
J Clin Oncol 2019 Nov 20;37(33):3142-3151. Epub 2019 Oct 3 doi: 10.1200/JCO.19.00489. PMID: 31580757Free PMC Article
Response to Anti-EGFR Therapy in Patients with BRAF non-V600-Mutant Metastatic Colorectal Cancer.
Yaeger R, Kotani D, Mondaca S, Parikh AR, Bando H, Van Seventer EE, Taniguchi H, Zhao H, Thant CN, de Stanchina E, Rosen N, Corcoran RB, Yoshino T, Yao Z, Ebi H
Clin Cancer Res 2019 Dec 1;25(23):7089-7097. Epub 2019 Sep 12 doi: 10.1158/1078-0432.CCR-19-2004. PMID: 31515458Free PMC Article
First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study.
Sullivan RJ, Infante JR, Janku F, Wong DJL, Sosman JA, Keedy V, Patel MR, Shapiro GI, Mier JW, Tolcher AW, Wang-Gillam A, Sznol M, Flaherty K, Buchbinder E, Carvajal RD, Varghese AM, Lacouture ME, Ribas A, Patel SP, DeCrescenzo GA, Emery CM, Groover AL, Saha S, Varterasian M, Welsch DJ, Hyman DM, Li BT
Cancer Discov 2018 Feb;8(2):184-195. Epub 2017 Dec 15 doi: 10.1158/2159-8290.CD-17-1119. PMID: 29247021

Prognosis

Clinical Activity of Mitogen-Activated Protein Kinase-Targeted Therapies in Patients With Non-V600 BRAF-Mutant Tumors.
Dankner M, Wang Y, Fazelzad R, Johnson B, Nebhan CA, Dagogo-Jack I, Myall NJ, Richtig G, Bracht JWP, Gerlinger M, Shinozaki E, Yoshino T, Kotani D, Fangusaro JR, Gautschi O, Mazieres J, Sosman JA, Kopetz S, Subbiah V, Davies MA, Groover AL, Sullivan RJ, Flaherty KT, Johnson DB, Benedetti A, Cescon DW, Spreafico A, Zogopoulos G, Rose AAN
JCO Precis Oncol 2022 Aug;6:e2200107. doi: 10.1200/PO.22.00107. PMID: 35977349Free PMC Article
Targeting BRAF-mutant non-small cell lung cancer: Current status and future directions.
Riudavets M, Cascetta P, Planchard D
Lung Cancer 2022 Jul;169:102-114. Epub 2022 May 26 doi: 10.1016/j.lungcan.2022.05.014. PMID: 35696864
Targeted Therapy in Advanced Melanoma With Rare BRAF Mutations.
Menzer C, Menzies AM, Carlino MS, Reijers I, Groen EJ, Eigentler T, de Groot JWB, van der Veldt AAM, Johnson DB, Meiss F, Schlaak M, Schilling B, Westgeest HM, Gutzmer R, Pföhler C, Meier F, Zimmer L, Suijkerbuijk KPM, Haalck T, Thoms KM, Herbschleb K, Leichsenring J, Menzer A, Kopp-Schneider A, Long GV, Kefford R, Enk A, Blank CU, Hassel JC
J Clin Oncol 2019 Nov 20;37(33):3142-3151. Epub 2019 Oct 3 doi: 10.1200/JCO.19.00489. PMID: 31580757Free PMC Article
Response to Anti-EGFR Therapy in Patients with BRAF non-V600-Mutant Metastatic Colorectal Cancer.
Yaeger R, Kotani D, Mondaca S, Parikh AR, Bando H, Van Seventer EE, Taniguchi H, Zhao H, Thant CN, de Stanchina E, Rosen N, Corcoran RB, Yoshino T, Yao Z, Ebi H
Clin Cancer Res 2019 Dec 1;25(23):7089-7097. Epub 2019 Sep 12 doi: 10.1158/1078-0432.CCR-19-2004. PMID: 31515458Free PMC Article
Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations.
Dankner M, Rose AAN, Rajkumar S, Siegel PM, Watson IR
Oncogene 2018 Jun;37(24):3183-3199. Epub 2018 Mar 15 doi: 10.1038/s41388-018-0171-x. PMID: 29540830

Clinical prediction guides

Pathways and targeting avenues of BRAF in non-small cell lung cancer.
Imyanitov EN, Mitiushkina NV, Kuligina ES, Tiurin VI, Venina AR
Expert Opin Ther Targets 2024 Jul;28(7):613-622. Epub 2024 Jul 4 doi: 10.1080/14728222.2024.2374742. PMID: 38941191
Clinical Activity of Mitogen-Activated Protein Kinase-Targeted Therapies in Patients With Non-V600 BRAF-Mutant Tumors.
Dankner M, Wang Y, Fazelzad R, Johnson B, Nebhan CA, Dagogo-Jack I, Myall NJ, Richtig G, Bracht JWP, Gerlinger M, Shinozaki E, Yoshino T, Kotani D, Fangusaro JR, Gautschi O, Mazieres J, Sosman JA, Kopetz S, Subbiah V, Davies MA, Groover AL, Sullivan RJ, Flaherty KT, Johnson DB, Benedetti A, Cescon DW, Spreafico A, Zogopoulos G, Rose AAN
JCO Precis Oncol 2022 Aug;6:e2200107. doi: 10.1200/PO.22.00107. PMID: 35977349Free PMC Article
Targeting BRAF-mutant non-small cell lung cancer: Current status and future directions.
Riudavets M, Cascetta P, Planchard D
Lung Cancer 2022 Jul;169:102-114. Epub 2022 May 26 doi: 10.1016/j.lungcan.2022.05.014. PMID: 35696864
Response to Anti-EGFR Therapy in Patients with BRAF non-V600-Mutant Metastatic Colorectal Cancer.
Yaeger R, Kotani D, Mondaca S, Parikh AR, Bando H, Van Seventer EE, Taniguchi H, Zhao H, Thant CN, de Stanchina E, Rosen N, Corcoran RB, Yoshino T, Yao Z, Ebi H
Clin Cancer Res 2019 Dec 1;25(23):7089-7097. Epub 2019 Sep 12 doi: 10.1158/1078-0432.CCR-19-2004. PMID: 31515458Free PMC Article
Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations.
Dankner M, Rose AAN, Rajkumar S, Siegel PM, Watson IR
Oncogene 2018 Jun;37(24):3183-3199. Epub 2018 Mar 15 doi: 10.1038/s41388-018-0171-x. PMID: 29540830

Recent systematic reviews

Clinical Activity of Mitogen-Activated Protein Kinase-Targeted Therapies in Patients With Non-V600 BRAF-Mutant Tumors.
Dankner M, Wang Y, Fazelzad R, Johnson B, Nebhan CA, Dagogo-Jack I, Myall NJ, Richtig G, Bracht JWP, Gerlinger M, Shinozaki E, Yoshino T, Kotani D, Fangusaro JR, Gautschi O, Mazieres J, Sosman JA, Kopetz S, Subbiah V, Davies MA, Groover AL, Sullivan RJ, Flaherty KT, Johnson DB, Benedetti A, Cescon DW, Spreafico A, Zogopoulos G, Rose AAN
JCO Precis Oncol 2022 Aug;6:e2200107. doi: 10.1200/PO.22.00107. PMID: 35977349Free PMC Article

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