NF1 Mutation

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Anaplastic Astrocytoma2
NF1 Mutation AND Methylation signature PA-NF1	(diagnostic)	Diagnostic	B	Supports Positive	4	submitted	EID12268 This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC	civic
NF1 Mutation AND Methylation signature PA-NF1	Selumetinib	Predictive	C	Supports Sensitivity Response	3	submitted	EID12270 This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Anaplastic Astrocytoma2

NF1 Mutation AND Methylation signature PA-NF1

(diagnostic)

Diagnostic

Supports Positive

submitted

EID12268

This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC)

PMID 35945463 · Lucas et al., 2022 · Open in CIViC

civic

NF1 Mutation AND Methylation signature PA-NF1

Selumetinib

Predictive

Supports Sensitivity Response

submitted

EID12270

PMID 35945463 · Lucas et al., 2022 · Open in CIViC

Childhood Low Grade Glioma1
NF1 Mutation	Selumetinib	Predictive	B	Supports Sensitivity Response	3	accepted	EID7487 In a phase 2 trial, patients with pediatric low-grade glioma after at least one standard therapy were treated with MEK1/2 inhibitor selumetinib. In stratum 1, nine patients with WHO grade I pilocytic … (full text at CIViC) PMID 31151904 · Fangusaro et al., 2019 · Open in CIViC	civic

Childhood Low Grade Glioma1

NF1 Mutation

Selumetinib

Predictive

Supports Sensitivity Response

accepted

EID7487

In a phase 2 trial, patients with pediatric low-grade glioma after at least one standard therapy were treated with MEK1/2 inhibitor selumetinib. In stratum 1, nine patients with WHO grade I pilocytic … (full text at CIViC)

PMID 31151904 · Fangusaro et al., 2019 · Open in CIViC

civic

Cutaneous Melanoma4
NF1 Mutation	Mirdametinib + SirolimusCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID1469 Preclinical study of mouse melanoma both in-vitro and in-vivo. Braf/Nf1-mutant melanomas were less sensitive to vemurafenib than the MEK inhibitor PD0325901. mTOR inhibition with rapamycin had a more … (full text at CIViC) PMID 23171796 · Maertens et al., 2013 · Open in CIViC	civic
NF1 Mutation	Vemurafenib	Predictive	C	Supports Resistance	4	accepted	EID1470 NF1 was identified in an unbiased RNAi screen as mediator of resistance to BRAF inhibition in BRAF mutant melanoma. Knockdown of NF1 led to PLX4720 resistance in-vitro. MEK inhibition with AZD6244 (se… (full text at CIViC) PMID 23288408 · Whittaker et al., 2013 · Open in CIViC	civic
NF1 Mutation	Vemurafenib	Predictive	D	Supports Resistance	2	accepted	EID1468 Preclinical study of mouse melanoma in-vitro and in-vivo. In-vitro treament of Braf-mutant melanomas were 10-fold more sensitive to vermurafenib (PLX4032) treatment than Braf/Nf1-mutant melanomas. In … (full text at CIViC) PMID 23171796 · Maertens et al., 2013 · Open in CIViC	civic
NF1 Mutation	AZ628 + VTX-11eSubstitutes	Predictive	D	Supports Sensitivity Response	2	accepted	EID1471 NF1 was identified in an unbiased RNAi screen as mediator of resistance to BRAF inhibition in BRAF mutant melanoma. BRAF V600E/NF1 mutant cell lines were sensitive to ERK inhibition with VTX-11e, mode… (full text at CIViC) PMID 23288408 · Whittaker et al., 2013 · Open in CIViC	civic

Cutaneous Melanoma4

NF1 Mutation

Mirdametinib + SirolimusCombination

Predictive

Supports Sensitivity Response

accepted

EID1469

Preclinical study of mouse melanoma both in-vitro and in-vivo. Braf/Nf1-mutant melanomas were less sensitive to vemurafenib than the MEK inhibitor PD0325901. mTOR inhibition with rapamycin had a more … (full text at CIViC)

PMID 23171796 · Maertens et al., 2013 · Open in CIViC

civic

NF1 Mutation

Vemurafenib

Predictive

Supports Resistance

accepted

EID1470

NF1 was identified in an unbiased RNAi screen as mediator of resistance to BRAF inhibition in BRAF mutant melanoma. Knockdown of NF1 led to PLX4720 resistance in-vitro. MEK inhibition with AZD6244 (se… (full text at CIViC)

PMID 23288408 · Whittaker et al., 2013 · Open in CIViC

civic

NF1 Mutation

Vemurafenib

Predictive

Supports Resistance

accepted

EID1468

Preclinical study of mouse melanoma in-vitro and in-vivo. In-vitro treament of Braf-mutant melanomas were 10-fold more sensitive to vermurafenib (PLX4032) treatment than Braf/Nf1-mutant melanomas. In … (full text at CIViC)

PMID 23171796 · Maertens et al., 2013 · Open in CIViC

civic

NF1 Mutation

AZ628 + VTX-11eSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID1471

NF1 was identified in an unbiased RNAi screen as mediator of resistance to BRAF inhibition in BRAF mutant melanoma. BRAF V600E/NF1 mutant cell lines were sensitive to ERK inhibition with VTX-11e, mode… (full text at CIViC)

PMID 23288408 · Whittaker et al., 2013 · Open in CIViC

civic

Lung Adenocarcinoma1
RIT1 Mutation OR NF1 Mutation	(diagnostic)	Diagnostic	B	Supports Positive	5	submitted	EID11373 This study contained 230 patients with untreated lung adenocarcinoma. Whole-exome sequencing of tumor cells yielded that RTK/RAS/RAF based mutations to be 62%. However, analysis shows that NF1 mutatio… (full text at CIViC) PMID 25079552 · 2014, Nature · Open in CIViC	civic

Lung Adenocarcinoma1

RIT1 Mutation OR NF1 Mutation

(diagnostic)

Diagnostic

Supports Positive

submitted

EID11373

This study contained 230 patients with untreated lung adenocarcinoma. Whole-exome sequencing of tumor cells yielded that RTK/RAS/RAF based mutations to be 62%. However, analysis shows that NF1 mutatio… (full text at CIViC)

PMID 25079552 · 2014, Nature · Open in CIViC

civic

Lung Non-Small Cell Carcinoma1
NF1 Mutation	Trametinib	Predictive	D	Supports Sensitivity Response	3	submitted	EID6054 Approximately 2% of NSCLCs had RASA1 truncating mutations, and this alteration was statistically, but not completely, mutually exclusive with known activating EGFR (p=0.02) and KRAS (p=0.02) mutations… (full text at CIViC) PMID 29127119 · Hayashi et al., 2018 · Open in CIViC	civic

Lung Non-Small Cell Carcinoma1

NF1 Mutation

Trametinib

Predictive

Supports Sensitivity Response

submitted

EID6054

Approximately 2% of NSCLCs had RASA1 truncating mutations, and this alteration was statistically, but not completely, mutually exclusive with known activating EGFR (p=0.02) and KRAS (p=0.02) mutations… (full text at CIViC)

PMID 29127119 · Hayashi et al., 2018 · Open in CIViC

civic

Malignant Neoplasm2
BRAF V600E OR NRAS Mutation OR HRAS Mutation OR KRAS Mutation OR NF1 Mutation	Selumetinib	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID11681 In this phase II study of the arm E of the NCI-COG pediatric MATCH trial, 20 patients (median age: 14) were treated with Selumetinib. High-grade glioma (n=7) and rhabdomyosarcoma (n=7) were the most c… (full text at CIViC) PMID 35363510 · Eckstein et al., 2022 · Open in CIViC	civic
NF1 Mutation OR GNA11 Q209L	Trametinib	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID12027 In this phase 2 clinical trial, 50 patients were treated with trametinib, a MEK1/2 inhibitor. Among them, 46 had tumours harbouring NF1 mutations (S1 protocol), while 4 had non-uveal melanomas harbour… (full text at CIViC) PMID 37053535 · Wisinski et al., 2023 · Open in CIViC	civic

Malignant Neoplasm2

BRAF V600E OR NRAS Mutation OR HRAS Mutation OR KRAS Mutation OR NF1 Mutation

Selumetinib

Predictive

Does Not Support Sensitivity Response

accepted

EID11681

In this phase II study of the arm E of the NCI-COG pediatric MATCH trial, 20 patients (median age: 14) were treated with Selumetinib. High-grade glioma (n=7) and rhabdomyosarcoma (n=7) were the most c… (full text at CIViC)

PMID 35363510 · Eckstein et al., 2022 · Open in CIViC

civic

NF1 Mutation OR GNA11 Q209L

Trametinib

Predictive

Does Not Support Sensitivity Response

accepted

EID12027

In this phase 2 clinical trial, 50 patients were treated with trametinib, a MEK1/2 inhibitor. Among them, 46 had tumours harbouring NF1 mutations (S1 protocol), while 4 had non-uveal melanomas harbour… (full text at CIViC)

PMID 37053535 · Wisinski et al., 2023 · Open in CIViC

civic

Neurofibroma1
NF1 Mutation	Tipifarnib	Predictive	B	Does Not Support Sensitivity Response	4	submitted	EID7426 In a randomized phase 2 trial, patient with neurofibromatosis type 1 (NF1) related progressive plexiform neurofibromatomas was allocated to farnesyltransferase inhibitor tipifarnib or placebo. Tipifar… (full text at CIViC) PMID 24500418 · Widemann et al., 2014 · Open in CIViC	civic

Neurofibroma1

NF1 Mutation

Tipifarnib

Predictive

Does Not Support Sensitivity Response

submitted

EID7426

In a randomized phase 2 trial, patient with neurofibromatosis type 1 (NF1) related progressive plexiform neurofibromatomas was allocated to farnesyltransferase inhibitor tipifarnib or placebo. Tipifar… (full text at CIViC)

PMID 24500418 · Widemann et al., 2014 · Open in CIViC

civic

Pilocytic Astrocytoma3
NF1 Mutation	(predisposing)	Predisposing	C	Supports Predisposition	2	rejected	EID12272 This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC	civic
NF1 Mutation AND Methylation signature PA-NF1	(diagnostic)	Diagnostic	B	Supports Positive	4	rejected	EID12267 This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC	civic
NF1 Mutation AND Methylation signature PA-NF1	Trametinib	Predictive	C	Supports Sensitivity Response	3	submitted	EID12269 This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC	civic

Pilocytic Astrocytoma3

NF1 Mutation

(predisposing)

Predisposing

Supports Predisposition

rejected

EID12272

PMID 35945463 · Lucas et al., 2022 · Open in CIViC

civic

NF1 Mutation AND Methylation signature PA-NF1

(diagnostic)

Diagnostic

Supports Positive

rejected

EID12267

PMID 35945463 · Lucas et al., 2022 · Open in CIViC

civic

NF1 Mutation AND Methylation signature PA-NF1

Trametinib

Predictive

Supports Sensitivity Response

submitted

EID12269

PMID 35945463 · Lucas et al., 2022 · Open in CIViC

civic

Plexiform Neurofibroma3
NF1 Mutation	Selumetinib	Predictive	A	Supports Sensitivity Response	3	accepted	EID1958 Treatment with selumetinib (NCT01362803) resulted in confirmed partial, long term responses in 17 of the 24 children with NF1 associated plexiform fibromas (71%) and decreases from baseline in neurofi… (full text at CIViC) PMID 28029918 · Dombi et al., 2016 · Open in CIViC	civic
NF1 Mutation	Selumetinib	Predictive	A	Supports Sensitivity Response	4	accepted	EID11176 In a pediatric phase 2 trial of the MEK inhibitor selumetinib (NCT01362803), partial responses were seen in 70% (35 of 50) children with neurofibromatosis type 1 and symptomatic inoperable plexiform n… (full text at CIViC) PMID 32187457 · Gross et al., 2020 · Open in CIViC	civic
NF1 Mutation	Selumetinib	Predictive	B	Supports Sensitivity Response	4	submitted	EID7266 Patients with Neurofibromatosis 1, inoperable Plexiform Neurofibroma and disease related morbidity received selumetinib. Best response PR (36 pts, 72%), stable disease (12 pts, 24%); 2 subjects (4%) h… (full text at CIViC) Open in CIViC	civic

Plexiform Neurofibroma3

NF1 Mutation

Selumetinib

Predictive

Supports Sensitivity Response

accepted

EID1958

Treatment with selumetinib (NCT01362803) resulted in confirmed partial, long term responses in 17 of the 24 children with NF1 associated plexiform fibromas (71%) and decreases from baseline in neurofi… (full text at CIViC)

PMID 28029918 · Dombi et al., 2016 · Open in CIViC

civic

NF1 Mutation

Selumetinib

Predictive

Supports Sensitivity Response

accepted

EID11176

In a pediatric phase 2 trial of the MEK inhibitor selumetinib (NCT01362803), partial responses were seen in 70% (35 of 50) children with neurofibromatosis type 1 and symptomatic inoperable plexiform n… (full text at CIViC)

PMID 32187457 · Gross et al., 2020 · Open in CIViC

civic

NF1 Mutation

Selumetinib

Predictive

Supports Sensitivity Response

submitted

EID7266

Patients with Neurofibromatosis 1, inoperable Plexiform Neurofibroma and disease related morbidity received selumetinib. Best response PR (36 pts, 72%), stable disease (12 pts, 24%); 2 subjects (4%) h… (full text at CIViC)

Open in CIViC

civic

Evidence by cancer (18 items)

Clinical significance (0)