ALK F1174L

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Anaplastic Large Cell Lymphoma1
ALK F1174L AND NPM1::ALK Fusion	Ceritinib	Predictive	D	Supports Resistance	3	submitted	EID12658 In an in vitro study, a FL5.12 cell line expressing NPM1-ALK (a known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated resistance to ceritinib treatment (IC50: 140.45 … (full text at CIViC) PMID 27009859 · Amin et al., 2016 · Open in CIViC	civic
Inflammatory Myofibroblastic Tumor1
ALK F1174L AND RANBP2::ALK Fusion	Crizotinib	Predictive	C	Supports Resistance	3	accepted	EID32 In a patient with RANBP2::ALK-positive inflammatory myofibroblastic tumor, acquisition of the ALK F1174L mutation following crizotinib treatment was associated with acquired resistance. Ba/F3 studies … (full text at CIViC)

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Anaplastic Large Cell Lymphoma1

ALK F1174L AND NPM1::ALK Fusion

Ceritinib

Predictive

Supports Resistance

submitted

EID12658

In an in vitro study, a FL5.12 cell line expressing NPM1-ALK (a known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated resistance to ceritinib treatment (IC50: 140.45 … (full text at CIViC)

PMID 27009859 · Amin et al., 2016 · Open in CIViC

civic

Inflammatory Myofibroblastic Tumor1

ALK F1174L AND RANBP2::ALK Fusion

Crizotinib

Predictive

Supports Resistance

accepted

EID32

In a patient with RANBP2::ALK-positive inflammatory myofibroblastic tumor, acquisition of the ALK F1174L mutation following crizotinib treatment was associated with acquired resistance. Ba/F3 studies … (full text at CIViC)

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
217851	Pathogenic	no assertion criteria provided	0	Neuroblastoma, susceptibility to, 3	somatic	1	Oct 07, 2015	clinvar

Variation

Clinical significance

Review status

Stars

Conditions

Origin

Submitters

Last evaluated

Source

217851

Pathogenic

no assertion criteria provided

Neuroblastoma, susceptibility to, 3

somatic

Oct 07, 2015

clinvar

Lung Large Cell Carcinoma1
ALK F1174L AND NPM1::ALK Fusion	Crizotinib	Predictive	D	Supports Resistance	2	submitted	EID4041 In an in vitro study, a FL5.12 cell line expressing NPM1-ALK (a known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated resistance to crizotinib treatment (IC50: 347.63… (full text at CIViC) PMID 27009859 · Amin et al., 2016 · Open in CIViC	civic

Lung Large Cell Carcinoma1

ALK F1174L AND NPM1::ALK Fusion

Crizotinib

Predictive

Supports Resistance

submitted

EID4041

In an in vitro study, a FL5.12 cell line expressing NPM1-ALK (a known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated resistance to crizotinib treatment (IC50: 347.63… (full text at CIViC)

PMID 27009859 · Amin et al., 2016 · Open in CIViC

civic

Lung Non-Small Cell Carcinoma1
EML4::ALK Fusion AND ALK F1174L	Crizotinib	Predictive	D	Supports Resistance	3	accepted	EID33 Ba/F3 cells expressing the EML4-ALK fusion containing an F1174L mutation were more resistant to crizotinib treatment than Ba/F3 cells expressing EML4-ALK without this mutation. PMID 21030459 · Sasaki et al., 2010 · Open in CIViC	civic

Lung Non-Small Cell Carcinoma1

EML4::ALK Fusion AND ALK F1174L

Crizotinib

Predictive

Supports Resistance

accepted

EID33

Ba/F3 cells expressing the EML4-ALK fusion containing an F1174L mutation were more resistant to crizotinib treatment than Ba/F3 cells expressing EML4-ALK without this mutation.

PMID 21030459 · Sasaki et al., 2010 · Open in CIViC

civic

Malignant Neoplasm5
ALK F1174L AND NPM1::ALK Fusion	Alectinib	Predictive	D	Supports Resistance	2	submitted	EID12665 In an in vitro study, a FL5.12 cell line expressing NPM-ALK (known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated increased resistance to alectinib treatment (IC50: … (full text at CIViC) PMID 27009859 · Amin et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK F1174L	Alectinib	Predictive	D	Does Not Support Resistance	2	submitted	EID12666 In an in vitro study, a FL5.12 cell line expressing EML4-ALK (known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated similar sensitivity to alectinib treatment (IC50: … (full text at CIViC) PMID 27009859 · Amin et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK F1174L	ALK Inhibitor ASP3026	Predictive	D	Supports Resistance	2	submitted	EID12676 In an in vitro study, a FL5.12 cell line expressing EML4-ALK (known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated increased resistance to ASP3026 treatment (IC50: 1… (full text at CIViC) PMID 27009859 · Amin et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK F1174L	AZD3463	Predictive	D	Does Not Support Resistance	2	submitted	EID12682 In an in vitro study, a FL5.12 cell line expressing EML4-ALK (known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated similar sensitivity to AZD3463 treatment (IC50: 15… (full text at CIViC) PMID 27009859 · Amin et al., 2016 · Open in CIViC	civic
EML4::ALK Fusion AND ALK F1174L	Crizotinib	Predictive	D	Does Not Support Resistance	2	submitted	EID12655 In an in vitro study, a FL5.12 cell line expressing EML4-ALK (known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated similar sensitivity to crizotinib treatment (IC50:… (full text at CIViC) PMID 27009859 · Amin et al., 2016 · Open in CIViC	civic

Malignant Neoplasm5

ALK F1174L AND NPM1::ALK Fusion

Alectinib

Predictive

Supports Resistance

submitted

EID12665

In an in vitro study, a FL5.12 cell line expressing NPM-ALK (known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated increased resistance to alectinib treatment (IC50: … (full text at CIViC)

PMID 27009859 · Amin et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK F1174L

Alectinib

Predictive

Does Not Support Resistance

submitted

EID12666

In an in vitro study, a FL5.12 cell line expressing EML4-ALK (known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated similar sensitivity to alectinib treatment (IC50: … (full text at CIViC)

PMID 27009859 · Amin et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK F1174L

ALK Inhibitor ASP3026

Predictive

Supports Resistance

submitted

EID12676

In an in vitro study, a FL5.12 cell line expressing EML4-ALK (known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated increased resistance to ASP3026 treatment (IC50: 1… (full text at CIViC)

PMID 27009859 · Amin et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK F1174L

AZD3463

Predictive

Does Not Support Resistance

submitted

EID12682

In an in vitro study, a FL5.12 cell line expressing EML4-ALK (known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated similar sensitivity to AZD3463 treatment (IC50: 15… (full text at CIViC)

PMID 27009859 · Amin et al., 2016 · Open in CIViC

civic

EML4::ALK Fusion AND ALK F1174L

Crizotinib

Predictive

Does Not Support Resistance

submitted

EID12655

In an in vitro study, a FL5.12 cell line expressing EML4-ALK (known sensitizing alteration to crizotinib) and an ALK F1174L co-mutation, demonstrated similar sensitivity to crizotinib treatment (IC50:… (full text at CIViC)

PMID 27009859 · Amin et al., 2016 · Open in CIViC

civic

Neuroblastoma9
ALK F1174L	Alectinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID37 CH5424802 (Alectinib) is effective in inhibiting the activity of the F1174L ALK mutant in a kinase activity assay and proliferation assay using neuroblastoma KELLY cells. PMID 21575866 · Sakamoto et al., 2011 · Open in CIViC	civic
ALK F1174L	ALK Inhibitor TAE684	Predictive	D	Supports Sensitivity Response	4	accepted	EID142 SH-SY5Y and Kelly cells with mutant ALK (F1174L) and Ba/F3 cells overexpressing ALK harboring the F1174L mutation are sensitive to TAE684-mediated growth inhibition. PMID 18923525 · George et al., 2008 · Open in CIViC	civic
ALK F1174L	AZD3463	Predictive	D	Supports Sensitivity Response	3	accepted	EID1327 The SH-SY5Y neuroblastoma cell line containing the F1174L ALK mutation was found to undergo cell death when treated with the ALK/IGF1R inhibitor AZD3463. These cells were more sensitive than other neu… (full text at CIViC) PMID 26786851 · Wang et al., 2016 · Open in CIViC	civic
ALK F1174L	Crizotinib	Predictive	B	Supports Resistance	—	rejected	EID2344 Activating mutations in the (ALK) gene are targeted by the dual-specific tyrosine kinase inhibitor crizotinib. The amino acid substitution F1174L resulted in a reduced response to crizotinib compared … (full text at CIViC) PMID 22072639 · Bresler et al., 2011 · Open in CIViC	civic
ALK F1174L	Crizotinib	Predictive	B	Supports Resistance	—	submitted	EID2345 Activating mutations in the (ALK) gene are targeted by the dual-specific tyrosine kinase inhibitor crizotinib. The amino acid substitution F1174L resulted in a reduced response to crizotinib compared … (full text at CIViC) PMID 21838707 · Schönherr et al., 2011 · Open in CIViC	civic
ALK F1174L	Crizotinib	Predictive	C	Does Not Support Sensitivity Response	3	accepted	EID1271 In a Phase I trial (NCT00939770) of the drug crizotinib in pediatric patients, a subset of 11 neuroblastoma patients were characterized for mutations in ALK. Of these 11 patients, 4 had the F1174L mut… (full text at CIViC) PMID 23598171 · Mossé et al., 2013 · Open in CIViC	civic
ALK F1174L	Crizotinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID38 High levels of crizotinib can overcome drug resistance of Ba/F3 cells expressing the EML4-ALK fusion containing the F1174L mutation. PMID 21948233 · Heuckmann et al., 2011 · Open in CIViC	civic
ALK F1174L	Crizotinib	Predictive	D	Supports Resistance	3	accepted	EID125 Cells lines expressing ALK harboring the F1174L mutation are less sensitive to growth inhibition by crizotinib than cells expressing the R1275Q mutation. The authors conclude that this effect should b… (full text at CIViC) PMID 22072639 · Bresler et al., 2011 · Open in CIViC	civic
ALK F1174L	Lorlatinib	Predictive	D	Supports Sensitivity Response	4	accepted	EID1329 Efficacy of the second generation ALK inhibitor PF-06463922 was tested on ALK mutation F1174L containing neuroblastoma-derived cells. COG-N-453x and SH-SY5Y xenografts showed some inhibition when tre… (full text at CIViC) PMID 26554404 · Infarinato et al., 2016 · Open in CIViC	civic

Neuroblastoma9

ALK F1174L

Alectinib

Predictive

Supports Sensitivity Response

accepted

EID37

CH5424802 (Alectinib) is effective in inhibiting the activity of the F1174L ALK mutant in a kinase activity assay and proliferation assay using neuroblastoma KELLY cells.

PMID 21575866 · Sakamoto et al., 2011 · Open in CIViC

civic

ALK F1174L

ALK Inhibitor TAE684

Predictive

Supports Sensitivity Response

accepted

EID142

SH-SY5Y and Kelly cells with mutant ALK (F1174L) and Ba/F3 cells overexpressing ALK harboring the F1174L mutation are sensitive to TAE684-mediated growth inhibition.

PMID 18923525 · George et al., 2008 · Open in CIViC

civic

ALK F1174L

AZD3463

Predictive

Supports Sensitivity Response

accepted

EID1327

The SH-SY5Y neuroblastoma cell line containing the F1174L ALK mutation was found to undergo cell death when treated with the ALK/IGF1R inhibitor AZD3463. These cells were more sensitive than other neu… (full text at CIViC)

PMID 26786851 · Wang et al., 2016 · Open in CIViC

civic

ALK F1174L

Crizotinib

Predictive

Supports Resistance

—

rejected

EID2344

Activating mutations in the (ALK) gene are targeted by the dual-specific tyrosine kinase inhibitor crizotinib. The amino acid substitution F1174L resulted in a reduced response to crizotinib compared … (full text at CIViC)

PMID 22072639 · Bresler et al., 2011 · Open in CIViC

civic

ALK F1174L

Crizotinib

Predictive

Supports Resistance

—

submitted

EID2345

PMID 21838707 · Schönherr et al., 2011 · Open in CIViC

civic

ALK F1174L

Crizotinib

Predictive

Does Not Support Sensitivity Response

accepted

EID1271

In a Phase I trial (NCT00939770) of the drug crizotinib in pediatric patients, a subset of 11 neuroblastoma patients were characterized for mutations in ALK. Of these 11 patients, 4 had the F1174L mut… (full text at CIViC)

PMID 23598171 · Mossé et al., 2013 · Open in CIViC

civic

ALK F1174L

Crizotinib

Predictive

Supports Sensitivity Response

accepted

EID38

High levels of crizotinib can overcome drug resistance of Ba/F3 cells expressing the EML4-ALK fusion containing the F1174L mutation.

PMID 21948233 · Heuckmann et al., 2011 · Open in CIViC

civic

ALK F1174L

Crizotinib

Predictive

Supports Resistance

accepted

EID125

Cells lines expressing ALK harboring the F1174L mutation are less sensitive to growth inhibition by crizotinib than cells expressing the R1275Q mutation. The authors conclude that this effect should b… (full text at CIViC)

PMID 22072639 · Bresler et al., 2011 · Open in CIViC

civic

ALK F1174L

Lorlatinib

Predictive

Supports Sensitivity Response

accepted

EID1329

Efficacy of the second generation ALK inhibitor PF-06463922 was tested on ALK mutation F1174L containing neuroblastoma-derived cells. COG-N-453x and SH-SY5Y xenografts showed some inhibition when tre… (full text at CIViC)

PMID 26554404 · Infarinato et al., 2016 · Open in CIViC

civic

Evidence by cancer (18 items)

Clinical significance (1)