NRAS Q61K

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Acral Lentiginous Melanoma1
NRAS Q61K	Belvarafenib	Predictive	C	Supports Sensitivity Response	2	accepted	EID13218 A patient with acral melanoma harboring NRAS Q61K received belvarafenib as first-line therapy for metastatic disease after progression on adjuvant pembrolizumab and achieved stable disease as the best… (full text at CIViC) PMID 38470950 · Kim et al., 2024 · Open in CIViC	civic
Cutaneous Melanoma3
NRAS Q61K	Selumetinib	Predictive	D	Supports Sensitivity Response	2	accepted	EID1475 Preclinical study in melanoma cell lines. NRAS Q61K, in addition to the BRAF V600E mutation was associated with resistance to vemurafenib but sensitivity to AZD6244 (selumetinib) in vitro in the acqui… (full text at CIViC) PMID 22194965 ·

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Acral Lentiginous Melanoma1

NRAS Q61K

Belvarafenib

Predictive

Supports Sensitivity Response

accepted

EID13218

A patient with acral melanoma harboring NRAS Q61K received belvarafenib as first-line therapy for metastatic disease after progression on adjuvant pembrolizumab and achieved stable disease as the best… (full text at CIViC)

PMID 38470950 · Kim et al., 2024 · Open in CIViC

civic

Cutaneous Melanoma3

NRAS Q61K

Selumetinib

Predictive

Supports Sensitivity Response

accepted

EID1475

Preclinical study in melanoma cell lines. NRAS Q61K, in addition to the BRAF V600E mutation was associated with resistance to vemurafenib but sensitivity to AZD6244 (selumetinib) in vitro in the acqui… (full text at CIViC)

PMID 22194965 ·

Lung Non-Small Cell Carcinoma2
NRAS Q61K	Erlotinib	Predictive	D	Supports Resistance	—	submitted	EID3839 In an in vitro study, a PC-9 cell line expressing NRAS Q61K mutation demonstrated decreased sensitivity to erlotinib treatment compared to PC-9 cells expressing NRAS wild-type. Sensitivity was determi… (full text at CIViC) PMID 22773810 · Ohashi et al., 2012 · Open in CIViC	civic
NRAS Q61K	Selumetinib + TrametinibSubstitutes	Predictive	D	Supports Sensitivity Response	2	accepted	EID2907 Of the 4,562 patients with lung cancers, 30 showed NRAS mutations, which corresponded to 9 different amino acid substitutions. Cell lines were developed for 6 of these mutations (one harboring Q61L, t… (full text at CIViC) PMID 23515407 · Ohashi et al., 2013 · Open in CIViC	civic

Lung Non-Small Cell Carcinoma2

NRAS Q61K

Erlotinib

Predictive

Supports Resistance

—

submitted

EID3839

In an in vitro study, a PC-9 cell line expressing NRAS Q61K mutation demonstrated decreased sensitivity to erlotinib treatment compared to PC-9 cells expressing NRAS wild-type. Sensitivity was determi… (full text at CIViC)

PMID 22773810 · Ohashi et al., 2012 · Open in CIViC

civic

NRAS Q61K

Selumetinib + TrametinibSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID2907

Of the 4,562 patients with lung cancers, 30 showed NRAS mutations, which corresponded to 9 different amino acid substitutions. Cell lines were developed for 6 of these mutations (one harboring Q61L, t… (full text at CIViC)

PMID 23515407 · Ohashi et al., 2013 · Open in CIViC

civic

Malignant Colorectal Neoplasm8
NRAS Q61K	Cetuximab	Predictive	B	Supports Resistance	—	submitted	EID3833 In 11 melanoma patients harboring BRAF mutations, one patient with a Q61K NRAS mutation acquired resistance to the BRAF inhibitor vemurafenib. Q61K and/or A146T NRAS mutations have also shown resista… (full text at CIViC) PMID 21107323 · Nazarian et al., 2010 · Open in CIViC	civic
NRAS Q61K	Cetuximab	Predictive	D	Supports Resistance	—	submitted	EID3834 In 28 out of 40 (70%) metastatic colorectal cancer tumors implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabiliza… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic
NRAS Q61K	Cetuximab + ChemotherapyCombination	Predictive	C	Supports Resistance	3	accepted	EID2189 Four patients participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored NRAS Q61K and were wildtype for KRAS, BRAF and P… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
NRAS Q61K	Dactolisib	Predictive	B	Supports Sensitivity Response	—	submitted	EID2194 In 11 melanoma patients harboring BRAF mutations, one patient with a Q61K NRAS mutation acquired resistance to the BRAF inhibitor vemurafenib. Q61K and/or A146T NRAS mutations have also shown resista… (full text at CIViC) PMID 21107323 · Nazarian et al., 2010 · Open in CIViC	civic
NRAS Q61K	Dactolisib	Predictive	C	Supports Sensitivity Response	—	rejected	EID2195 NRAS mutations have also been observed in melanoma and biliary tract, bladder, cervix, liver, lung, myeloid leukemia, ovarian, pancreatic, and thyroid cancer. PMID 17384584 · Schubbert et al., 2007 · Open in CIViC	civic
NRAS Q61K	Dactolisib	Predictive	D	Supports Sensitivity Response	—	submitted	EID2196 In 28 out of 40 (70%) metastatic colorectal cancer tumors implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabiliza… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic
NRAS Q61K	Dactolisib + SelumetinibCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID2192 In 28 out of 40 (70%) metastatic colorectal cancer tumors harboring mutations in KRAS, NRAS, BRAF, or PIK3CA and implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the P… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic
NRAS Q61K	Selumetinib	Predictive	C	Supports Sensitivity Response	—	rejected	EID2190 NRAS mutations have also been observed in melanoma and biliary tract, bladder, cervix, liver, lung, myeloid leukemia, ovarian, pancreatic, and thyroid cancer. PMID 17384584 · Schubbert et al., 2007 · Open in CIViC	civic

Malignant Colorectal Neoplasm8

NRAS Q61K

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3833

In 11 melanoma patients harboring BRAF mutations, one patient with a Q61K NRAS mutation acquired resistance to the BRAF inhibitor vemurafenib. Q61K and/or A146T NRAS mutations have also shown resista… (full text at CIViC)

PMID 21107323 · Nazarian et al., 2010 · Open in CIViC

civic

NRAS Q61K

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3834

In 28 out of 40 (70%) metastatic colorectal cancer tumors implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabiliza… (full text at CIViC)

PMID 22392911 · Migliardi et al., 2012 · Open in CIViC

civic

NRAS Q61K

Cetuximab + ChemotherapyCombination

Predictive

Supports Resistance

accepted

EID2189

Four patients participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored NRAS Q61K and were wildtype for KRAS, BRAF and P… (full text at CIViC)

PMID 20619739 · De Roock et al., 2010 · Open in CIViC

civic

NRAS Q61K

Dactolisib

Predictive

Supports Sensitivity Response

—

submitted

EID2194

PMID 21107323 · Nazarian et al., 2010 · Open in CIViC

civic

NRAS Q61K

Dactolisib

Predictive

Supports Sensitivity Response

—

rejected

EID2195

NRAS mutations have also been observed in melanoma and biliary tract, bladder, cervix, liver, lung, myeloid leukemia, ovarian, pancreatic, and thyroid cancer.

PMID 17384584 · Schubbert et al., 2007 · Open in CIViC

civic

NRAS Q61K

Dactolisib

Predictive

Supports Sensitivity Response

—

submitted

EID2196

PMID 22392911 · Migliardi et al., 2012 · Open in CIViC

civic

NRAS Q61K

Dactolisib + SelumetinibCombination

Predictive

Supports Sensitivity Response

accepted

EID2192

In 28 out of 40 (70%) metastatic colorectal cancer tumors harboring mutations in KRAS, NRAS, BRAF, or PIK3CA and implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the P… (full text at CIViC)

PMID 22392911 · Migliardi et al., 2012 · Open in CIViC

civic

NRAS Q61K

Selumetinib

Predictive

Supports Sensitivity Response

—

rejected

EID2190

NRAS mutations have also been observed in melanoma and biliary tract, bladder, cervix, liver, lung, myeloid leukemia, ovarian, pancreatic, and thyroid cancer.

PMID 17384584 · Schubbert et al., 2007 · Open in CIViC

civic

Malignant Lung Neoplasm1
NRAS Q61K	Selumetinib + Trametinib	Predictive	D	Supports Sensitivity Response	3	rejected	EID2908 NRAS mutations define a distinct subset of lung cancers (∼1%) with potential sensitivity to MEK inhibitors. Although NRAS mutations are more common in current/former smokers, the types of mutations ar… (full text at CIViC) PMID 23515407 · Ohashi et al., 2013 · Open in CIViC	civic

Malignant Lung Neoplasm1

NRAS Q61K

Selumetinib + Trametinib

Predictive

Supports Sensitivity Response

rejected

EID2908

NRAS mutations define a distinct subset of lung cancers (∼1%) with potential sensitivity to MEK inhibitors. Although NRAS mutations are more common in current/former smokers, the types of mutations ar… (full text at CIViC)

PMID 23515407 · Ohashi et al., 2013 · Open in CIViC

civic

Malignant Neoplasm3
NRAS Q61K	Trametinib	Predictive	D	Supports Sensitivity Response	3	submitted	EID12456 Cell lines were treated with varying concentrations of trametinib for 3 days. Viability was measured by ATP-Glo. The lung large cell carcinoma cell line, H1299 (NRAS Q61K), was sensitive with a low IC… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
NRAS Q61K AND BRAF G466V	Cetuximab	Predictive	D	Supports Resistance	3	submitted	EID12450 Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab as measured by cell growth and RAS-GT… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
NRAS Q61K AND BRAF G466V	Trametinib	Predictive	D	Does Not Support Resistance	3	submitted	EID12451 Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab but not trametinib as measured by cel… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic

Malignant Neoplasm3

NRAS Q61K

Trametinib

Predictive

Supports Sensitivity Response

submitted

EID12456

Cell lines were treated with varying concentrations of trametinib for 3 days. Viability was measured by ATP-Glo. The lung large cell carcinoma cell line, H1299 (NRAS Q61K), was sensitive with a low IC… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic

NRAS Q61K AND BRAF G466V

Cetuximab

Predictive

Supports Resistance

submitted

EID12450

Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab as measured by cell growth and RAS-GT… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic

NRAS Q61K AND BRAF G466V

Trametinib

Predictive

Does Not Support Resistance

submitted

EID12451

Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab but not trametinib as measured by cel… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic

Malignant Ovarian Serous Tumor1
NRAS Q61K	Trametinib	Predictive	C	Supports Sensitivity Response	2	accepted	EID8933 One 56 year old female with advanced recurrent low grade serous ovarian cancer with NRAS Q61K mutation had a partial response to trametinib, with short follow-up. PMID 30809568 · Champer et al., 2019 · Open in CIViC	civic

Malignant Ovarian Serous Tumor1

NRAS Q61K

Trametinib

Predictive

Supports Sensitivity Response

accepted

EID8933

One 56 year old female with advanced recurrent low grade serous ovarian cancer with NRAS Q61K mutation had a partial response to trametinib, with short follow-up.

PMID 30809568 · Champer et al., 2019 · Open in CIViC

civic

Melanoma8
NRAS Q61K	(predisposing)	Predisposing	D	Supports Likely Pathogenic	4	submitted	EID7169 Established a novel mouse model for melanoma that shows for the first time that over expression of a mutant form of human N-ras (N-RasQ61K) in melanocytes results in a hyper pigmented skin phenotype a… (full text at CIViC) PMID 15899789 · Ackermann et al., 2005 · Open in CIViC	civic
NRAS Q61K	(predisposing)	Predisposing	D	Supports Likely Pathogenic	4	submitted	EID7172 Recent studies in mouse have also shown that NRAS Q61K is capable of promoting melanoma formation and cooperates with INK4A loss to accelerate tumor onset. PMID 19954345 · Dovey et al., 2009 · Open in CIViC	civic
NRAS Q61K	Belvarafenib	Predictive	C	Supports Resistance	2	submitted	EID13217 Two patients with NRAS Q61K-mutant melanoma treated with belvarafenib had progressive disease as their best RECIST response. One patient progressed after 1.6 months and the other after 1.4 months of t… (full text at CIViC) PMID 38470950 · Kim et al., 2024 · Open in CIViC	civic
NRAS Q61K	Dabrafenib + TrametinibCombination	Predictive	B	Supports Resistance	4	submitted	EID7678 In a retrospective study, authors analyzed BRAF V600 mutated melanoma metastases derived from 10 patients treated with the combination of dabrafenib and trametinib for resistance mechanisms and geneti… (full text at CIViC) PMID 25452114 · Long et al., 2014 · Open in CIViC	civic
NRAS Q61K	Vemurafenib	Predictive	C	Supports Resistance	4	submitted	EID2191 In 11 melanoma patients harboring BRAF mutations, one patient with a Q61K NRAS mutation acquired resistance to the BRAF inhibitor vemurafenib. Q61K and/or A146T NRAS mutations have also shown resistan… (full text at CIViC) PMID 21107323 · Nazarian et al., 2010 · Open in CIViC	civic
NRAS Q61K	Vemurafenib	Predictive	C	Supports Resistance	—	submitted	EID3835 In a retrospective study of 44 malignant melanoma patients, NRAS Q61K was associated with acquired resistance to vemurafenib monotherapy in two patients with disease progressive tumors harboring NRAS … (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic
NRAS Q61K	Vemurafenib	Predictive	D	Supports Resistance	—	submitted	EID3836 In an in vitro study, a M249 cell line expressing BRAF V600E (a known sensitizing mutation to vemurafenib) and NRAS Q61K co-mutations, demonstrated resistance to vemurafenib treatment (GI50: > 10 �mol… (full text at CIViC) PMID 21107323 · Nazarian et al., 2010 · Open in CIViC	civic
NRAS Q61K	Vemurafenib	Predictive	D	Supports Resistance	—	submitted	EID3837 In an in vitro study, a M249 R4 cell line expressing BRAF V600E (a known sensitizing mutation to vemurafenib) and NRAS Q61K co-mutations demonstrated acquired resistance to vemurafenib treatment. Resi… (full text at CIViC) PMID 22395615 · Shi et al., 2012 · Open in CIViC	civic

Melanoma8

NRAS Q61K

(predisposing)

Predisposing

Supports Likely Pathogenic

submitted

EID7169

Established a novel mouse model for melanoma that shows for the first time that over expression of a mutant form of human N-ras (N-RasQ61K) in melanocytes results in a hyper pigmented skin phenotype a… (full text at CIViC)

PMID 15899789 · Ackermann et al., 2005 · Open in CIViC

civic

NRAS Q61K

(predisposing)

Predisposing

Supports Likely Pathogenic

submitted

EID7172

Recent studies in mouse have also shown that NRAS Q61K is capable of promoting melanoma formation and cooperates with INK4A loss to accelerate tumor onset.

PMID 19954345 · Dovey et al., 2009 · Open in CIViC

civic

NRAS Q61K

Belvarafenib

Predictive

Supports Resistance

submitted

EID13217

Two patients with NRAS Q61K-mutant melanoma treated with belvarafenib had progressive disease as their best RECIST response. One patient progressed after 1.6 months and the other after 1.4 months of t… (full text at CIViC)

PMID 38470950 · Kim et al., 2024 · Open in CIViC

civic

NRAS Q61K

Dabrafenib + TrametinibCombination

Predictive

Supports Resistance

submitted

EID7678

In a retrospective study, authors analyzed BRAF V600 mutated melanoma metastases derived from 10 patients treated with the combination of dabrafenib and trametinib for resistance mechanisms and geneti… (full text at CIViC)

PMID 25452114 · Long et al., 2014 · Open in CIViC

civic

NRAS Q61K

Vemurafenib

Predictive

Supports Resistance

submitted

EID2191

PMID 21107323 · Nazarian et al., 2010 · Open in CIViC

civic

NRAS Q61K

Vemurafenib

Predictive

Supports Resistance

—

submitted

EID3835

In a retrospective study of 44 malignant melanoma patients, NRAS Q61K was associated with acquired resistance to vemurafenib monotherapy in two patients with disease progressive tumors harboring NRAS … (full text at CIViC)

PMID 24265155 · Shi et al., 2014 · Open in CIViC

civic

NRAS Q61K

Vemurafenib

Predictive

Supports Resistance

—

submitted

EID3836

In an in vitro study, a M249 cell line expressing BRAF V600E (a known sensitizing mutation to vemurafenib) and NRAS Q61K co-mutations, demonstrated resistance to vemurafenib treatment (GI50: > 10 �mol… (full text at CIViC)

PMID 21107323 · Nazarian et al., 2010 · Open in CIViC

civic

NRAS Q61K

Vemurafenib

Predictive

Supports Resistance

—

submitted

EID3837

In an in vitro study, a M249 R4 cell line expressing BRAF V600E (a known sensitizing mutation to vemurafenib) and NRAS Q61K co-mutations demonstrated acquired resistance to vemurafenib treatment. Resi… (full text at CIViC)

PMID 22395615 · Shi et al., 2012 · Open in CIViC

civic

Neuroblastoma1
NRAS Q61K	Binimetinib + EverolimusCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID1002 In-vitro study in 5 neuroblastoma cell lines (2 with NRAS Q61K mutation). The combination of mTOR and MEK Inhibitors synergistically blocked cell growth in NRAS mutant but not wild type cell lines. Si… (full text at CIViC) PMID 26821351 · Kiessling et al., 2016 · Open in CIViC	civic

Neuroblastoma1

NRAS Q61K

Binimetinib + EverolimusCombination

Predictive

Supports Sensitivity Response

accepted

EID1002

In-vitro study in 5 neuroblastoma cell lines (2 with NRAS Q61K mutation). The combination of mTOR and MEK Inhibitors synergistically blocked cell growth in NRAS mutant but not wild type cell lines. Si… (full text at CIViC)

PMID 26821351 · Kiessling et al., 2016 · Open in CIViC

civic

Evidence by cancer (28 items)

Clinical significance (0)