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EGFR
Variants
VariantGeneTypeCOSMIC IDDNA Change (Coding Nucleotide)Exon
EGFR L858REGFRmissenseCOSM62242573T>G21
EGFR P546SEGFRmissenseCOSM12380721636C>T14
EGFR S492REGFRmissenseCOSM2366701476C>A12
EGFR T790MEGFRmissenseCOSM62402369C>T20
EGFR T854AEGFRmissenseCOSM285372560A>G21
EGFR A289VEGFRmissense7
EGFR A289DEGFRmissense7
EGFR G598VEGFRmissense15
EGFR P596LEGFRmissense15
EGFR codon(s) 289, 596, 598 anyEGFRany7, 15, 15
EGFR exon(s) 18, 19, 20, 21 anyEGFRany18, 19, 20, 21
EGFR E746_A750delinsIEGFRindel2238_2250delinsATT19
EGFR exon(s) 19 deletionEGFRdeletion19
EGFR codon(s) 790 anyEGFRany20
EGFR exon(s) 20 anyEGFRany20
EGFR H773LEGFRmissense20
EGFR V774MEGFRmissense20
EGFR D761NEGFRmissense19
EGFR D761YEGFRmissense19
EGFR codon(s) 761 anyEGFRany19
EGFR G863DEGFRmissense21
EGFR P753SEGFRmissense19
EGFR L861QEGFRmissense21
EGFR codon(s) 861 anyEGFRany21
EGFR E709KEGFRmissense2125G>A18
EGFR exon(s) 20 insertionEGFRinsertion20
EGFR copy number gainEGFRCNV
EGFR E746_A750delEGFRdeletion2235_2249del1519
EGFR S768IEGFRmissenseCOSM62412303G>T20
EGFR G724SEGFRmissenseCOSM139792170G>A18
EGFR R776HEGFRmissenseCOSM229402327G>A20
EGFR any missenseEGFRmissense
EGFR K745_E746insIPVAIKEGFRinsertionCOSM124232231_2232ins1819
EGFR E709_T710delinsDEGFRdeletion2127_2129delAAC18
EGFR exon(s) 18 indelEGFRindel18
EGFR exon(s) 18 deletionEGFRdeletion18
EGFR L747PEGFRmissenseCOSM242672239_2240TT>CC19
EGFR V769LEGFRmissenseCOSM62422305G>T20
EGFR R108KEGFRmissenseCOSM21683323G>A3
EGFR L861REGFRmissense2582T>G21
EGFR L747_T751delinsSEGFRdeletion2240_2251del1219
EGFR A750PEGFRmissenseCOSM62192248G>C19
EGFR A763_Y764insFQEAEGFRinsertionCOSM267202290_2291ins1220
EGFR G719AEGFRmissenseCOSM62392156G>C18
EGFR G719CEGFRmissenseCOSM62532155G>T18
EGFR G719DEGFRmissenseCOSM184252156G>A18
EGFR G719SEGFRmissenseCOSM62522155G>A18
EGFR L833VEGFRmissenseCOSM134242497T>G21
EGFR copy number lossEGFRCNV
EGFR any mutationEGFRany
EGFR G721SEGFRmissense18
EGFR K757MEGFRmissense19
EGFR V765MEGFRmissense20
EGFR K745_E746insTPVAIKEGFRinsertionCOSM25515219
EGFR K745_E746insVPVAIKEGFRinsertionCOSM2644419
EGFR H773_V774delinsLMEGFRindel20
EGFR E709_G719delins11EGFRindel18
EGFR G796SEGFRmissenseCOSM2089120

Interpretations

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Tier 2
EGFR
Variants
Primary Sites
Blood
Bone Marrow
Tumor Types
Acute Myeloid Leukemia
Interpretation

Despite pre-clinical data and case reports of response to EGFR inhibitors, the EGFR inhibitor gefitinib does not appear to be effective in the treatment of advanced AML .

Last updated: 2016-06-05 02:44:56 UTC
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Tier 2
EGFR
Variants
EGFR A289V
EGFR A289D
EGFR G598V
EGFR P596L
EGFR codon(s) 289, 596, 598 any
Primary Sites
Spinal Cord
Brain
Brain, Supratentorial
Brain, Infratentorial
Tumor Types
Glioblastoma
Interpretation

EGFR mutations in GBM cluster in the extracellular (EC) domain and include in-frame deletions (such as the common “variant III” del 6-273) and missense mutations (A289V, A289D, T263P, G598V). In vitro and in vivo studies reveal anchorage-independent growth and tumorigenic potential when the A289 and G598 variants are stably expressed in NIH-3T3 cells. The A289 and G598 mutations sensitize Ba/F3 cells to erlotinib in vitro according to some reports, although other reports state glioma-specific EGFR EC mutants are poorly inhibited by EGFR inhibitors that target the active kinase conformation (e.g., erlotinib). The A289 variant has been reported to show sensitivity towards BAY846, a tyrosine kinase inhibitor in brain tumors. In addition, according to some reports, inhibitors which bind to the inactive EGFR conformation potently inhibit EGFR EC mutants and induce cell death in EGFR mutant GBM cells.

Last updated: 2015-12-09 20:15:19 UTC
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Tier 1
EGFR
Variants
EGFR L858R
EGFR exon(s) 18, 19, 20, 21 any
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to EGFR inhibitors. Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR Exon 19 deletions , EGFR Exon 21 L858R and EGFR Exon 18 G719 mutations correlate strongly with sensitivity to specific EGFR inhibitors and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. The T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. However, third generation TKI (eg, osimertinib) can specifically target T790M.

Last updated: 2021-10-19 15:34:57 UTC
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Tier 1
EGFR
Variants
EGFR E746_A750delinsI
EGFR exon(s) 19 deletion
EGFR E746_A750del
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR inhibitors (eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR Exon 19 deletions , EGFR Exon 21 L858R and EGFR Exon 18 G719 mutations correlate strongly with sensitivity to specific EGFR inhibitors and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. The T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. However, third generation TKI (eg, osimertinib) can specifically target T790M. Erlotinib Afatinib Gefitinib Osimertinib

Last updated: 2018-04-06 14:53:53 UTC
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Tier 1
EGFR
Variants
EGFR codon(s) 790 any
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR inhibitors (eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR Exon 19 deletions , EGFR Exon 21 L858R and EGFR Exon 18 G719 mutations correlate strongly with sensitivity to specific EGFR inhibitors and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. The T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. However, third generation TKI (eg, osimertinib) can specifically target T790M.

Last updated: 2017-04-10 19:21:46 UTC
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Tier 3
EGFR
Variants
EGFR exon(s) 20 any
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

EGFR D770N in Exon 20 has been reported. The significance is unknown.

Last updated: 2015-12-09 20:15:45 UTC
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Tier 1
EGFR
Variants
EGFR exon(s) 20 insertion
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

EGFR exon 20 insertion testing identifies a distinct subset of lung adenocarcinomas, accounting for at least 9% of all EGFR-mutated cases and by molecular modeling, are predicted to have potentially different effects on erlotinib binding. Studies show that in contrast to the more classic activating EGFR mutations, these insertions have been associated with de novo resistance to approved EGFR-TKIs (erlotinib and gefitinib). In a recent study, patients with advanced lung adenocarcinoma harboring exon 20 insertions demonstrated no response or partial response following treatment with TK inhibitors. Exon 20 insertion mutations in EGFR may be associated with clinical trials (https://clinicaltrials.gov/).

Last updated: 2018-03-06 17:56:01 UTC
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Tier 1
EGFR
Variants
EGFR H773L
EGFR V774M
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

EGFR exon 20 insertion testing identifies a distinct subset of lung adenocarcinomas, accounting for at least 9% of all EGFR-mutated cases and by molecular modeling, are predicted to have potentially different effects on erlotinib binding. Studies show that in contrast to the more classic activating EGFR mutations, these insertions have been associated with de novo resistance to approved EGFR-TKIs (erlotinib and gefitinib). In a recent study, patients with advanced lung adenocarcinoma harboring exon 20 insertions demonstrated no response or partial response following treatment with TK inhibitors. This rare complex mutation (p.H773_V774delinsLM) results in the H773L/V774 mutation compound at the same allele, potentially weakening the inactive state and leading to constitutional activation of EGFR. A recent clinical report suggests this mutation is insensitive to the reversible TKI gefitinib, but can be suppressed by the irreversible TKI osimertinib, leading to sustained disease control (Yang et al., Lung Cancer, 121:1-4, 2018). Exon 20 insertion mutations in EGFR may be associated with clinical trials (https://clinicaltrials.gov/).

Last updated: 2019-01-22 18:50:26 UTC
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Tier 2
EGFR
Variants
EGFR exon(s) 20 insertion
Primary Sites
Brain
Spinal Cord
Brain, Supratentorial
Brain, Infratentorial
Tumor Types
Glioblastoma
Interpretation

In GBM, EGFR mutations typically cluster in the extracellular domain and include in-frame deletions (such as the common “variant III” del 6-273) and missense mutations (A289V, A289D, T263P, G598V). EGFR exon 20 insertions have not been previously reported in GBM. The clinical significance of this mutation with regards to response to anti-EGFR therapy in GBM is unknown. In general, EGFR exon 20 mutations have been reported in approximately 9% of all EGFR-mutated cases of lung cancer and studies show that in contrast to the more classic activating EGFR mutations, these insertions have been associated with de novo resistance or only partial response to approved EGFR-TKIs (erlotinib and gefitinib) in lung cancer.

Last updated: 2015-12-09 23:42:32 UTC
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Tier 1
EGFR
Variants
EGFR D761N
EGFR D761Y
EGFR codon(s) 761 any
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

The EGFR D761 mutation is associated with acquired resistance to EGFR-TKIs (Balak et al., 2006). The functional significance of this alteration is being investigated.

Last updated: 2015-12-09 20:16:10 UTC
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Tier 3
EGFR
Variants
EGFR G863D
Primary Sites
Lung
Stomach
Tumor Types
Adenocarcinoma
Interpretation

A low frequency mutation detected in lung and gastric cancer. Functional significance of this alteration has not yet been described. However, a single NSCLC patient with this mutation in a clinical trial shows partial response to gefitinb therapy

Last updated: 2015-12-09 20:16:16 UTC
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Tier 2
EGFR
Variants
EGFR P753S
Primary Sites
Skin
Tumor Types
Squamous Cell Carcinoma
Interpretation

It is unclear what effect the EGFR P753S varaints has on the EGFR protein. However the location of the variant in the splice site acceptor of Exon 19 may activate the kinase domain. The identification of the EGFR P735S mutation in the context of a dramatic response to cetuximab in a patient with cutaneous squamous cell carcinoma, indicates a new potential pairing of EGFR mutation and targeted therapy for patients with cSCC.

Last updated: 2015-12-09 20:16:21 UTC
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Tier 1
EGFR
Variants
EGFR L861Q
EGFR codon(s) 861 any
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR inhibitors (eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR Exon 19 deletions , EGFR Exon 21 L858R and EGFR Exon 18 G719 mutations correlate strongly with sensitivity to specific EGFR inhibitors and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. The L861Q mutation is one of the less common mutations which is an activating mutation that is believed to confer sensitivity to the targeted EGFR tyrosine kinase inhibitors although this mutation may confer reduced response to these inhibitors compared to the more common mutations.

Last updated: 2018-04-06 15:03:01 UTC
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Tier 1
EGFR
Variants
EGFR E709K
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

Compound (dual) mutations in EGFR have been previously reported in lung adenocarcinoma and typically include a strong activating mutation combined with a weaker activating mutation. These cases appear to respond well to the EGFR targetted therapies if they include mutations that are known to provide sensitivity to EGFR inhibitor therapies. L858R is a well known activating mutation in exon 21 that is associated with sensitivity to EGFR inhibitors. In vitro functional characterization of mutations at E709 have also been reported to be activivating mutations that are also associated with sensitivity to EGFR inhibitors in vitro. Mutations in E709 often occur together with other muations in EGFR including the L858R mutation.

Last updated: 2015-12-09 20:16:31 UTC
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Tier 2
EGFR
Variants
EGFR E709K
Primary Sites
Spinal Cord
Brain
Brain, Supratentorial
Brain, Infratentorial
Tumor Types
Glioblastoma
Interpretation

In GBM, EGFR mutations typically cluster in the extracellular domain and include in-frame deletions (such as the common “variant III” del 6-273) and missense mutations (A289V, A289D, T263P, G598V). However, the p.E709K mutation in the tyrosine kinase domain of EGFR has not been previously reported in GBM. In vitro functional characterization of mutations at E709 have been reported to be activivating mutations that are associated with sensitivity to EGFR inhibitors in vitro in some cell systems. The clinical significance of this mutation with regards to response to anti-EGFR therapy in GBM is unknown.

Last updated: 2015-12-09 20:16:31 UTC
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Tier 1
EGFR
Variants
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

Based on reports in the literature, EGFR and KRAS mutations can occasionally coexist in the same bronchial-pulmonary carcinoma. The biological implications of this coexistence are still poorly understood mainly because these cases are not frequent. It is therefore necessary to study larger series of cases with the two mutations to better understand the biological, clinical and therapeutic implications. Patients with coexisting EGFR and KRAS variants may have a partial response to EGFR TKI.

Last updated: 2015-12-09 21:32:55 UTC
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Tier 2
EGFR
Variants
EGFR copy number gain
Primary Sites
Brain
Brain, Infratentorial
Brain, Supratentorial
Tumor Types
Glioblastoma
Interpretation

Greater than 40% of glioblastomas (GBM) harbor focal amplification of the EGFR locus and there is evidence to suggest that these are driver alterations in these patients, making the EGFR pathway a potential therapeutic target in some clinical settings. Moreover, this alteration is relatively specific for GBM with very few other diffusely infiltrative gliomas having been shown to carry focal amplification of this locus (<3%). In GBM, this alteration frequently occurs in combination with other alterations of EGFR including polysomy 7, intragenic inframe deletions (e.g. EGFRvIII), and/or somatic point mutations. Based on current evidence, the independent predictive value of EGFR amplification in GBM is unclear. The relationship between individual and concurrent EGFR alterations and clinical response to small molecular inhibitors targeting EGFR is currently under investigation in clinical trials.

Last updated: 2016-10-11 21:41:07 UTC
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Tier 1
EGFR
Variants
EGFR copy number gain
Primary Sites
Bladder
Tumor Types
Urothelial Carcinoma
Interpretation

EGFR has been reported to show increased expression in a subset of bladder cancers and may be a targetable alteration in some clinical settings.

Last updated: 2016-02-18 04:07:15 UTC
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Tier 1
EGFR
Variants
EGFR S768I
EGFR G724S
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Squamous Cell Carcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR tyrosine kinase inhibitors (eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR Exon 19 deletions, EGFR Exon 21 L858R and EGFR Exon 18 G719 mutations correlate strongly with sensitivity to specific EGFR inhibitors and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. EGFR S768I (exon 20) occurs in 1–2% of EGFR mutant lung cancers and is often coincident with other EGFR mutations. EGFR S768I is reported to be sensitive to EGFR-TKIs. EGFR G724S (exon 18) is very rare and its significance is unknown.

Last updated: 2016-05-05 13:32:06 UTC
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Tier 2
EGFR
Variants
EGFR R776H
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

The epidermal growth factor receptor (EGFR) is a cell surface receptor belonging to the ErbB family tyrosine kinase receptors. EGFR is involved in cell growth control through its role in the two main intracellular pathways, the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase- (PI3K-) protein kinase B (AKT) pathway. The over-expression or mutation of EGFR may be responsible for the constitutive activation of these pathways. In the colorectal cancer, the EGFR has been found to be frequently over expressed, and may be associated with tumor stage and prognosis. In a subset of such patients, the addition of anti-EGFR monoclonal antibodies to the conventional chemotherapeutic regimens may expand response rates and increase progression-free survival. Somatic EGFR mutations are infrequent in colorectal cancers. The frequency varies from 0.34 to 3.3% in Western population, and from 12% to 22.4% in Asians. R776H is a recurrent mutation in the hinge region of the kinase domain and is known to activate EGFR in a ligand independent manner. In some cases, the possibility of R776H variant being of germline origin, cannot be excluded. The clinicopathologic correlation of EGFR mutations in colorectal cancers continues to be explored.

Last updated: 2016-05-05 13:40:13 UTC
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Tier 1
EGFR
Variants
EGFR K745_E746insIPVAIK
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Pleomorphic Carcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR inhibitors (eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR Exon 19 deletions, EGFR Exon 21 L858R and EGFR Exon 18 G719 mutations correlate strongly with sensitivity to specific EGFR inhibitors and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. The T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. However, third generation TKI (eg, osimertinib) can specifically target T790M. EGFR exon 19 in-frame insertions have been described in about 1% of EGFR-mutant lung cancers. They appear to be more common in nonsmoking women. These exon 19 insertions appear to be sensitizing mutations and have been shown to respond to TKIs in some studies.

Last updated: 2016-05-18 23:02:30 UTC
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Tier 1
EGFR
Variants
EGFR E709_T710delinsD
EGFR exon(s) 18 indel
EGFR exon(s) 18 deletion
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Non-Small Cell Lung Carcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR inhibitors (eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR Exon 19 deletions, EGFR Exon 21 L858R mutations correlate strongly with sensitivity to specific EGFR inhibitors and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. The T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. However, third generation TKI (eg, osimertinib) can specifically target T790M. EGFR exon 18 mutations account for 3.6% of all the EGFR mutations in lung adenocarcinomas. Of these, G719 mutations account for the majority of them and are sensitive to anti-EGFR inhibitors. Exon 18 deletions are rare (<0.1%) and but they are potentially responsive to anti-EGFR TKIs in some small clinical case studies. Of note, they appeared to be more sensitive to second-generation TKIs, especially afatinib and neratinib, than to first- and third-generation TKIs based on in vitro experiments.

Last updated: 2016-06-01 20:16:47 UTC
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Tier 1
EGFR
Variants
EGFR copy number gain
Primary Sites
Gastroesophageal Junction
Esophagus
Stomach
Tumor Types
Adenocarcinoma
Interpretation

Copy number gain (amplification) of EGFR has been reported in up to 30% of esophageal adenocarcinomas and less than 5% of gastric adenocarcinomas. According to some studies increased EGFR protein expression may be associated with decreased survival. This alteration may have therapeutic implications in some settings.

Last updated: 2016-06-01 21:09:54 UTC
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Tier 2
EGFR
Variants
EGFR T790M
Primary Sites
Stomach
Tumor Types
Adenocarcinoma
Squamous Cell Carcinoma
Interpretation

EGFR mutations have been reported in up to 5% of gastric cancers. The prognostic and predictive implications of EGFR mutations in gastric cancer have not been fully determined. Multiple clinical trials involving EGFR small molecule inhibitors and monoclonal antibodies are present, but limited and conflicting data preclude the therapeutic significance of EGFR mutations in gastric cancer. In NSCLC, an acquired T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. Third generation TKIs (e.g. osimertinib) have been shown to be effective in lung adenocarcinomas with the EGFR T790M mutation. A germline EGFR T790M mutation results in a rare lung cancer hereditary syndrome associated with increased risk in never-smokers. The presence of a germline EGFR T790M mutation also predicts for resistance to standard TKIs. The significance of EGFR T790M in gastric cancer should be considered in a relevant clinical context. Drug Resistance: Afatinib Erlotinib Gefitinib

Last updated: 2018-04-18 14:23:32 UTC
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Tier 1
EGFR
Variants
EGFR L747P
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Non-Small Cell Lung Carcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR inhibitors (eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR Exon 19 deletions, EGFR Exon 21 L858R and EGFR Exon 18 G719 mutations correlate strongly with sensitivity to specific EGFR inhibitors and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. The T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. However, third generation TKI (eg, osimertinib) can specifically target T790M. EGFR L747P (c.2239_2240 TT>CC) is a rare missense compound substitution mutation in the Exon 19 and has been reported to be resistant to some EGFR inhibitors.

Last updated: 2016-08-01 20:01:33 UTC
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Tier 2
EGFR
Variants
Primary Sites
Stomach
Tumor Types
Adenocarcinoma
Interpretation

EGFR mutations have been reported in up to 5% of gastric cancers. The prognostic and predictive implications of EGFR mutations in gastric cancer have not been fully determined. Multiple clinical trials involving EGFR small molecule inhibitors and monoclonal antibodies are present, but limited and conflicting data preclude the therapeutic significance of EGFR mutations in gastric cancer.

Last updated: 2016-10-11 21:48:32 UTC
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Tier 2
EGFR
Variants
Primary Sites
Thyroid
Tumor Types
Papillary Carcinoma
Follicular Carcinoma
Interpretation

EGFR mutations have been reported in 1-3% of thyroid cancers. The prognostic and predictive significance of EGFR mutations in thyroid cancer is not clear and correlation with other clinical and laboratory findings is necessary. Clinical trials involving protein kinase inhibitor are available for patients with tumors harboring EGFR mutations.

Last updated: 2016-08-31 22:11:48 UTC
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Tier 1
EGFR
Variants
EGFR copy number gain
Primary Sites
Colon
Rectum
Tumor Types
Carcinoma
Adenocarcinoma
Interpretation

In colorectal cancer, EGFR gene amplification is associated with sensitivity EGFR-targeted therapies, such as Erbitux and Vectibix.

Last updated: 2017-01-20 03:41:37 UTC
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Tier 2
EGFR
Variants
EGFR V774M
Primary Sites
Brain
Tumor Types
Glioblastoma
Interpretation

EGFR mutations have been reported in up to 21% of glioblastoma tumors (GBM). In GBM, EGFR mutations typically cluster in the extracellular domain and include in-frame deletions and missense mutations. However, mutations (such as V774M) in the tyrosine kinase domain of EGFR have been previously reported in GBM. The clinical significance of this mutation with regards to response to TKI therapy in GBM needs further elucidation. Results should be interpreted in conjunction with other laboratory and clinical findings.

Last updated: 2017-02-03 21:49:47 UTC
Read More
Tier 1
EGFR
Variants
EGFR S768I
EGFR V769L
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Non-Small Cell Lung Carcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR tyrosine kinase inhibitors (eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR Exon 19 deletions, EGFR Exon 21 L858R and EGFR Exon 18 G719 mutations correlate strongly with sensitivity to specific EGFR inhibitors and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. EGFR S768I (exon 20) occurs in 1–2% of EGFR mutant lung cancers and is often coincident with other EGFR mutations. S768I and V769L have previously been identified in the same NSCLC tumors. There are conflicting data regarding the sensitivity to EGFR-TKIs of tumors harboring S768I and V769L mutations. Correlation with other clinical and laboratory findings is necessary.

Last updated: 2017-04-10 18:14:01 UTC
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Tier 2
EGFR
Variants
EGFR R108K
Primary Sites
Brain
Tumor Types
Glioblastoma
Interpretation

EGFR mutations in GBM cluster in the extracellular (EC) domain and include in-frame deletions (such as the common “variant III” del 6-273) and missense mutations (A289V, A289D, T263P, G598V). Mutations involving residue R108 have been reported in GBM, frequently occurring with other EGFR mutations at amino acids A289, P596, and G598. In vitro studies have shown that R108K mutation leads to increased ligand-binding affinity and shows anchorage-independent growth and tumorigenic potential when stably expressed in NIH-3T3 cells. The predictive and prognostic significance of this mutation at R108 needs further elucidation. Correlation with other clinical and laboratory findings is recommended.

Last updated: 2017-04-17 23:17:37 UTC
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Tier 1
EGFR
Variants
EGFR L861R
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

Erlotinib Afatinib Gefitinib

Last updated: 2017-08-01 17:55:42 UTC
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Tier 2
EGFR
Variants
EGFR copy number gain
EGFR copy number loss
Primary Sites
Adrenal Gland
Anus
Ampulla (Pancreaticobiliary Duct)
Appendix
Bladder
Blood
Bone
Bone Marrow
Brain
Breast
Spinal Cord
Cervix
Chest Wall
Colon
Endometrium
Esophagus
Eye
Fallopian Tube
Fibroadipose Tissue
Gall Bladder
Kidney
Larynx
Liver
Lung
Lymph Node
Nasal Cavity
Oral Cavity
Ovary
Pancreas
Parathyroid
Penis
Peripheral Nervous System
Peritoneum
Pharynx
Pituitary
Placenta
Pleura
Prostate
Retroperitoneum
Salivary Gland
Seminal Vesicle
Skeletal Muscle
Skin
Small Intestine
Soft Tissue
Spleen
Stomach
Testis
Thymus
Thyroid
Tonsil
Unknown
Ureter
Uterus
Vagina
Rectum
Cartilage
Blood Vessel
Buccal Swab
Heart
Trachea
Salivary Duct
Spermatic Cord
Vulva
Brain, Infratentorial
Brain, Supratentorial
Gastroesophageal Junction
Sellar
Suprasellar
Peritoneal fluid
Pleural Fluid
Tongue
Tumor Types
Acinar Cell Carcinoma
Acinic Cell Carcinoma
Acute Myeloid Leukemia
Adenocarcinoma
Adenoid Cystic Carcinoma
Adenosarcoma
Ameloblastic Tumor
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-Cell Lymphoma
Angiomatoid Fibrous Histiocytoma
Angiomatosis
Angiomyolipoma
Angiosarcoma
Astrocytoma, Anaplastic
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
Basal Cell Carcinoma
Burkitt Lymphoma
Carcinoid Tumor
Carcinoma
Carcinosarcoma
Cholangiocarcinoma
Chondrosarcoma
Chordoma
Choriocarcinoma
Chromophobe Renal Cell Carcinoma
Chronic Lymphocytic Leukemia
Chronic Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Classical Hodgkin Lymphoma
Clear Cell Carcinoma
Clear Cell Renal Cell Carcinoma
Craniopharyngioma
Dermatofibrosarcoma
Desmoplastic Small Round Cell Tumor
Diffuse Large B Cell Lymphoma
Ductal Carcinoma
Ependymoma
Essential Thrombocythemia
Ewing Sarcoma
Fibromatosis
Follicular Carcinoma
Follicular Lymphoma
Gastrointestinal Stromal Tumor
Germ Cell Tumor
Giant Cell Tumor
Glioblastoma
Glomus Tumor
Granular Cell Tumor
Hairy Cell Leukemia
Hemangioendothelioma
Hepatocellular Carcinoma
Histiocytic and Dendritic Cell Neoplasms
Invasive Ductal Carcinoma
Kaposi Sarcoma
Langerhans Cell Histiocytosis
Leiomyoma
Leiomyosarcoma
Lipoma
Liposarcoma
Lobular Carcinoma
Lymphoplasmacytic Lymphoma
Malignant Mullerian Mixed Tumor
Mantle Cell Lymphoma
Marginal Zone B Cell Lymphoma
Mast Cell Neoplasm
MDS with Ring Sideroblasts
Medullary Carcinoma
Medulloblastoma
Melanoma
Meningioma
Merkel Cell Carcinoma
Mesothelioma
Mucinous Adenocarcinoma
Mucinous Tumors of Ovary
Mucoepidermoid Carcinoma
Myelodysplastic Syndrome
Myeloproliferative Neoplasm
Myxofibrosarcoma
Nasopharyngeal Carcinoma
Neuroblastoma
Neuroendocrine Carcinoma
Neuroendocrine Neoplasm
NK Cell Lymphoproliferative Disorder
NLPHL
Non-Small Cell Lung Carcinoma
Oligodendroglioma
Osteosarcoma
Papillary Carcinoma
Papillary Renal Cell Carcinoma
Peripheral T Cell Lymphoma
Pheochromocytoma
Plasma Cell Disorder
Polycythemia Vera
Post-Transplant Lymphoproliferative Disorder
Primary Myelofibrosis
Primitive Neuroectodermal Tumor
Renal Cell Carcinoma
Reninoma
Retinoblastoma
Rhabdomyosarcoma
Sarcoma
Schwannoma
Serous Carcinoma
Sex Cord Stromal Tumor
Small Cell Carcinoma
Solid Pseudopapillary Tumor of Pancreas
Spindle Cell Neoplasm
Squamous Cell Carcinoma
T Cell Lymphoproliferative Disorder
T Lymphoblastic Leukemia/Lymphoma
T-Cell LGL Leukemia
Thymic Carcinoma
Thymoma
Urothelial Carcinoma
Tumors of Peripheral Nerves
Unknown
Wilms Tumor
Ependymoma, Anaplastic
Astrocytoma, Pilocytic
Ganglioglioma
Neuroepithelial Neoplasm, NOS
Pleomorphic Carcinoma
Solitary Fibrous Tumor
Neuroepithelial neoplasm, high grade
Leukocytosis
Thrombocytosis
Monocytosis
Cytopenia
Other Acute Leukemia
Astrocytoma, NOS
Acute Leukemia of Unspecified Cell Type
Anemia, Unspecified
Astrocytoma, Diffusely Infiltrating
Diffuse Midline Glioma
Infiltrating Glioma, NOS
Intraductal Papillary Mucinous Neoplasm (IPMN)
Leukopenia
Lymphadenopathy
Lymphocytosis, Symptomatic
Monoclonal Gammopathy
Mucinous or Serous Cystic Neoplasms of Pancreas
Mycosis Fungoides, Unspecified Site
Oligodendroglioma, Anaplastic
Pleomorphic Xanthoastrocytoma
Rash and Other Nonspecific Skin Eruption
Thrombocytopenia, Unspecified
Eosinophilia
Myelodysplastic/Myeloproliferative Neoplasm
Myeloid Neoplasm
Polycythemia
Hurthle Cell Carcinoma
High Grade Glioma
Undifferentiated Sarcoma
Glioma
Interpretation

This gene is a known cancer gene.

Last updated: 2018-05-17 15:39:20 UTC
Read More
Tier 2
EGFR
Variants
EGFR any mutation
Primary Sites
Adrenal Gland
Anus
Ampulla (Pancreaticobiliary Duct)
Appendix
Bladder
Blood
Bone
Bone Marrow
Brain
Breast
Spinal Cord
Cervix
Chest Wall
Colon
Endometrium
Esophagus
Eye
Fallopian Tube
Fibroadipose Tissue
Gall Bladder
Kidney
Larynx
Liver
Lung
Lymph Node
Nasal Cavity
Oral Cavity
Ovary
Pancreas
Parathyroid
Penis
Peripheral Nervous System
Peritoneum
Pharynx
Pituitary
Placenta
Pleura
Prostate
Retroperitoneum
Salivary Gland
Seminal Vesicle
Skeletal Muscle
Skin
Small Intestine
Soft Tissue
Spleen
Stomach
Testis
Thymus
Thyroid
Tonsil
Unknown
Ureter
Uterus
Vagina
Rectum
Cartilage
Blood Vessel
Buccal Swab
Heart
Trachea
Salivary Duct
Spermatic Cord
Vulva
Brain, Infratentorial
Brain, Supratentorial
Gastroesophageal Junction
Sellar
Suprasellar
Peritoneal fluid
Pleural Fluid
Tongue
Tumor Types
Acinar Cell Carcinoma
Acinic Cell Carcinoma
Acute Myeloid Leukemia
Adenocarcinoma
Adenoid Cystic Carcinoma
Adenosarcoma
Ameloblastic Tumor
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-Cell Lymphoma
Angiomatoid Fibrous Histiocytoma
Angiomatosis
Angiomyolipoma
Angiosarcoma
Astrocytoma, Anaplastic
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
Basal Cell Carcinoma
Burkitt Lymphoma
Carcinoid Tumor
Carcinoma
Carcinosarcoma
Cholangiocarcinoma
Chondrosarcoma
Chordoma
Choriocarcinoma
Chromophobe Renal Cell Carcinoma
Chronic Lymphocytic Leukemia
Chronic Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Classical Hodgkin Lymphoma
Clear Cell Carcinoma
Clear Cell Renal Cell Carcinoma
Craniopharyngioma
Dermatofibrosarcoma
Desmoplastic Small Round Cell Tumor
Diffuse Large B Cell Lymphoma
Ductal Carcinoma
Ependymoma
Essential Thrombocythemia
Ewing Sarcoma
Fibromatosis
Follicular Carcinoma
Follicular Lymphoma
Gastrointestinal Stromal Tumor
Germ Cell Tumor
Giant Cell Tumor
Glioblastoma
Glomus Tumor
Granular Cell Tumor
Hairy Cell Leukemia
Hemangioendothelioma
Hepatocellular Carcinoma
Histiocytic and Dendritic Cell Neoplasms
Invasive Ductal Carcinoma
Kaposi Sarcoma
Langerhans Cell Histiocytosis
Leiomyoma
Leiomyosarcoma
Lipoma
Liposarcoma
Lobular Carcinoma
Lymphoplasmacytic Lymphoma
Malignant Mullerian Mixed Tumor
Mantle Cell Lymphoma
Marginal Zone B Cell Lymphoma
Mast Cell Neoplasm
MDS with Ring Sideroblasts
Medullary Carcinoma
Medulloblastoma
Melanoma
Meningioma
Merkel Cell Carcinoma
Mesothelioma
Mucinous Adenocarcinoma
Mucinous Tumors of Ovary
Mucoepidermoid Carcinoma
Myelodysplastic Syndrome
Myeloproliferative Neoplasm
Myxofibrosarcoma
Nasopharyngeal Carcinoma
Neuroblastoma
Neuroendocrine Carcinoma
Neuroendocrine Neoplasm
NK Cell Lymphoproliferative Disorder
NLPHL
Non-Small Cell Lung Carcinoma
Oligodendroglioma
Osteosarcoma
Papillary Carcinoma
Papillary Renal Cell Carcinoma
Peripheral T Cell Lymphoma
Pheochromocytoma
Plasma Cell Disorder
Polycythemia Vera
Post-Transplant Lymphoproliferative Disorder
Primary Myelofibrosis
Primitive Neuroectodermal Tumor
Renal Cell Carcinoma
Reninoma
Retinoblastoma
Rhabdomyosarcoma
Sarcoma
Schwannoma
Serous Carcinoma
Sex Cord Stromal Tumor
Small Cell Carcinoma
Solid Pseudopapillary Tumor of Pancreas
Spindle Cell Neoplasm
Squamous Cell Carcinoma
T Cell Lymphoproliferative Disorder
T Lymphoblastic Leukemia/Lymphoma
T-Cell LGL Leukemia
Thymic Carcinoma
Thymoma
Urothelial Carcinoma
Tumors of Peripheral Nerves
Unknown
Wilms Tumor
Ependymoma, Anaplastic
Astrocytoma, Pilocytic
Ganglioglioma
Neuroepithelial Neoplasm, NOS
Pleomorphic Carcinoma
Solitary Fibrous Tumor
Neuroepithelial neoplasm, high grade
Leukocytosis
Thrombocytosis
Monocytosis
Cytopenia
Other Acute Leukemia
Astrocytoma, NOS
Acute Leukemia of Unspecified Cell Type
Anemia, Unspecified
Astrocytoma, Diffusely Infiltrating
Diffuse Midline Glioma
Infiltrating Glioma, NOS
Intraductal Papillary Mucinous Neoplasm (IPMN)
Leukopenia
Lymphadenopathy
Lymphocytosis, Symptomatic
Monoclonal Gammopathy
Mucinous or Serous Cystic Neoplasms of Pancreas
Mycosis Fungoides, Unspecified Site
Oligodendroglioma, Anaplastic
Pleomorphic Xanthoastrocytoma
Rash and Other Nonspecific Skin Eruption
Thrombocytopenia, Unspecified
Eosinophilia
Myelodysplastic/Myeloproliferative Neoplasm
Myeloid Neoplasm
Polycythemia
Hurthle Cell Carcinoma
High Grade Glioma
Undifferentiated Sarcoma
Glioma
Interpretation

This gene is a known cancer gene.

Last updated: 2018-05-17 15:40:14 UTC
Read More
Tier 2
EGFR
Variants
EGFR V765M
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

The epidermal growth factor receptor (EGFR) is a cell surface receptor belonging to the ErbB family tyrosine kinase receptors. EGFR is involved in cell growth control through its role in the two main intracellular pathways, the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase- (PI3K-) protein kinase B (AKT) pathway. The over-expression or mutation of EGFR may be responsible for the constitutive activation of these pathways. In colorectal cancer, EGFR has been found to be frequently over expressed, and may be associated with tumor stage and prognosis. Somatic EGFR mutations are infrequent in colorectal cancers. The frequency of EGFR mutations in colorectal cancer varies from 0.34 to 3.3% in Western population, and from 12% to 22.4% in Asians. In a subset of patients with EGFR mutations in colorectal cancer, the addition of anti-EGFR monoclonal antibodies to the conventional chemotherapeutic regimens may expand response rates and increase progression-free survival. EGFR V765M lies within the protein kinase domain of the protein. In lung cancer, the V765M has been reported as a sensitizing mutation to EGFR tyrosine kinase inhibitors. The correlation of EGFR gene mutations with clinicopathologic characteristics in colorectal cancers continues to be explored.

Last updated: 2018-03-06 17:59:58 UTC
Read More
Tier 1
EGFR
Variants
EGFR K757M
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR inhibitors (eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR Exon 19 deletions, EGFR Exon 21 L858R and EGFR Exon 18 G719 mutations correlate strongly with sensitivity to specific EGFR inhibitors and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. The T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. However, third generation TKI (eg, osimertinib) can specifically target T790M. EGFR K757M has been reported as a rare variant lung adenocarcinoma, but the significance remains to be elucidated.

Last updated: 2018-03-06 18:00:24 UTC
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Tier 2
EGFR
Variants
EGFR G721S
Primary Sites
Prostate
Tumor Types
Adenocarcinoma
Interpretation

EGFR (HER1), epidermal growth factor receptor, is a tyrosine kinase receptor, which activates RAS/RAF/MEK and PI3K/AKT/mTOR pathways, leading to increased cell proliferation and growth. EGFR G721S lies within the protein kinase domain of the EGFR protein. G721S has been identified in the scientific literature in lung cancer, but has not been biochemically characterized and therefore, its effect on EGFR protein function is unknown. EGFR mutations are rare and in prostate adenocarcinoma and are identified in only about 1% of cases. The clinicopathologic significance of the EGFR G721S variant in prostate cancer remains to be fully elucidated.

Last updated: 2018-03-06 18:00:47 UTC
Read More
Tier 1
EGFR
Variants
EGFR E709K
Primary Sites
Lung
Tumor Types
Non-Small Cell Lung Carcinoma
Interpretation

Afatinib Erlotinib Gefitinib

Last updated: 2018-04-06 14:42:49 UTC
Read More
Tier 1
EGFR
Variants
EGFR A750P
Primary Sites
Lung
Tumor Types
Non-Small Cell Lung Carcinoma
Interpretation

Afatinib Erlotinib Gefitinib

Last updated: 2018-04-06 14:44:03 UTC
Read More
Tier 1
EGFR
Variants
EGFR A763_Y764insFQEA
Primary Sites
Lung
Tumor Types
Non-Small Cell Lung Carcinoma
Interpretation

Sensitive to: Afatinib Erlotinib Gefitinib

Last updated: 2018-04-06 14:49:59 UTC
Read More
Tier 1
EGFR
Variants
EGFR G719A
Primary Sites
Lung
Tumor Types
Non-Small Cell Lung Carcinoma
Interpretation

Afatinib Erlotinib Gefitinib AP32788

Last updated: 2018-04-06 14:54:39 UTC
Read More
Tier 1
EGFR
Variants
EGFR G719C
Primary Sites
Lung
Tumor Types
Non-Small Cell Lung Carcinoma
Interpretation

Afatinib Erlotinib Gefitinib

Last updated: 2018-04-06 15:07:27 UTC
Read More
Tier 1
EGFR
Variants
EGFR G719S
EGFR G719D
Primary Sites
Lung
Tumor Types
Non-Small Cell Lung Carcinoma
Interpretation

Afatinib Erlotinib Gefitinib

Last updated: 2018-12-27 19:19:21 UTC
Read More
Tier 1
EGFR
Variants
EGFR E709_G719delins11
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR inhibitors (eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR exon19 deletions, exon 21 L858R and Exon 18 mutations correlate strongly with sensitivity to specific EGFR inhibitors, and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. The T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. However, third generation TKI (eg, osimertinib) can specifically target T790M. Compound (dual) mutations in EGFR have been previously reported in lung adenocarcinoma and typically include a strong activating mutation combined with a weaker activating mutation. These cases appear to respond well to the EGFR targeted therapies. Mutations at E709 in exon 18 often occur together with other mutations in EGFR. This particular complex deletion insertion variant results in both the E709V and G719C in the protein, as well as a K713R variant, which also has been reported previously.

Last updated: 2019-02-22 18:04:20 UTC
Read More
Tier 2
EGFR
Variants
EGFR R108K
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR inhibitors (eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR Exon 19 deletions, EGFR Exon 21 L858R and EGFR Exon 18 G719 mutations correlate strongly with sensitivity to specific EGFR inhibitors and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. The T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. However, third generation TKI (eg, osimertinib) can specifically target T790M. EGFR R108K (C.323G>A) is a rare missense mutation in Exon 3. In a study of 1006 lung carcinomas, R108K mutation was found concomitantly with other EGFR mutations - most notably p.L858R (Illei et.al). However, its prognostic and therapeutic significance remains to be fully elucidated.

Last updated: 2019-02-22 18:07:41 UTC
Read More
Tier 1
EGFR
Variants
EGFR G796S
Primary Sites
Lung
Tumor Types
Non-Small Cell Lung Carcinoma
Adenocarcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR tyrosine kinase inhibitors (TKIs, eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. Exon 20 mutations are more commonly associated with resistance to tyrosine kinase inhibitors (TKIs), but may respond to third generation TKI (eg, osimertinib). This EGFR variant (G796S) lies within the tyrosine kinase domain and has been reported in rare cases of lung adenocarcinomas, squamous cell carcinoma of head and neck and prostate adenocarcinoma. In silico studies suggest G796S mutation may confer resistance to TKIs. However, additional studies are needed to further elucidate the oncogenicity of the mutation and therapeutic implications of this rare variant.

Last updated: 2019-07-15 15:39:26 UTC
Read More
PMKB Bot
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity

Disclaimer: You assume full responsibility for all risks associated with using this PMKB website. The Englander Institute for Precision Medicine at Weill Cornell Medicine makes no guarantee of the comprehensiveness, reliability or accuracy of the information on this website and assumes no responsibility for errors in the information associated with this web site. Healthcare providers and patients must integrate all clinical and laboratory findings as well as information from a variety of sources before deciding on appropriate clinical care options.


When using PMKB, please cite: Huang et al., JAMIA 2017


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