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EGFR Mutation Database

EGFR Mutation Database
Non small cell lung cancer (NSCLC) is one of the most common cancers worldwide. Pulmonary malignancies are the leading cause of death in both men and women.
 
The epidermal growth factor receptor (EGFR) is a tyrosine protein kinase. Activation of the downstream pathways of EGFR leads to cell proliferation, differentiation, migration/ motility, adhesion, protection from apoptosis, enhanced survival and gene transcription. A large body of experimental and clinical work supports the view that EGFR is a relevant target for cancer therapy.
 
Gefitinib (Iressa) and Erlotinib (Tarceva) are utilized for the treatment of refractory NSCLC due to the impressive response seen in about 10-15% of patients. Several recent publications reported that virtually all responders have a somatic mutation at a mutational "hotspot" within the kinase domain of the EGFR gene (Exons 18-21). 

The City of Hope Molecular Diagnostic Laboratory (MDL) was the first to introduce clinical testing for EGFR mutations (July 2004) for patients with lung cancer1. In an effort to facilitate the identification of structure/function and genotype/phenotype relationships,we created this EGFR Mutation Database website to provide a convenient listing of EGFR sequence variants reported in the scientific literature and their reported association with drug response. The papers with EGFR mutations are identified by searching NCBI PubMed quarterly.

EGFR Mutation Data

The EGFR gene is located at chromosomal locus 7p12.3-p12.1.

The EGFR Mutations table lists mutations reported in the scientific literature and their reported association with drug response. The cDNA sequence from GenBank Accession NM_005228.3 is used as the reference sequence. (click here for the annotated EGFR cDNA reference sequence)

The EGFR Polymorphisms table lists polymorphisms reported in the scientific literature and those polymorphisms from NCBI dbSNP that are found in exons and within 50 bases of an exon. The mRNA sequence from GeneBank Accession NM_005228.3 is used as the reference sequence. (click here for the annotated EGFR mRNA reference sequence)

Data Tables

EGFR Response Criteria, Ascertainment, Analysis Methods By Reference
( Printable pdfExcel format )

EGFR Mutation List Ordered By Reference
( Printable pdfExcel format )

EGFR Mutation List Ordered By Mutation
( Printable pdfExcel format )

EGFR Polymorphism List Ordered By Polymorphism Site
( Printable pdfExcel format

EGFR Mutation Statistics

EGFR Database Terms

Table 1. Field descriptions for the database of reported EGFR mutations in lung cancers.
 
Database Field Description
Patient ID Unique patient identification number in this database.
Exon Exon of the identified mutation.
Mutation Type Duplication, microdeletion, microindel (mutation that results
in a co-localized insertion and deletion and a net change in
size), micoinsertion, missense or nonsense.
Nucleotide change Numbering according to mRNA sequence NM_005228.3.
CpG Whether or not this nucleotide is part of a CpG dinucleotide
(Yes/No).
Amino Acid change Numbering according to protein sequence NP_005219.2.
Proven Somatic Whether mutation was confirmed to be somatic by analysis
of normal cells (Yes, No, Unknown).
Reference Article in which the mutation was originally published.
Patient No Patient ID from original publication, if available, otherwise a
generated ID based on treatment and mutation type.
Gender F, female; M, male.
Age Patient age at the time of specimen collection.
Ethnicity/Putative
Ethnicity
Ethnicity or Putative Ethnicity of the patient according to
the original publication.
Pathological Type Coded as ADC, Adenocarcinoma; BAC, Bronchioloalveolar
carcinoma; BWFI, BAC with focal invasion; AWFB,
Adenocarcinoma with BAC features; SCC, Squamous;
LCC, large cell carcinoma.
Smoking Status Listed as described in the original publication.
Treatment Gefitinib, Erlotinib
Response Criteria Criteria used to determine the patient response rate.
Response Response to treatment. CR – Complete Response; PR –
Partial Response; SD – Stable disease; PD – Progressive
Disease
Revisions Revisions or additions to the data or annotations reported
in the original publication including corrections to errors in
the original publication and the addition of new data
provided by the authors and not in the original publication.
Date Confirmed by
Author
Date on which the data was last confirmed by the author.


Table 2. Field descriptions for the database of reported germline polymorphisms in EGFR.

Database Field Description
Polymorphism ID Unique polymorphism identification number in this database.
Exon or Intron EGFR exon or intron number.
Variant Type Non-coding, missense or silent.
Nucleotide change Numbering according to cDNA sequence NM_005228.3.
Amino Acid change Numbering according to protein sequence NP_005219.2.
Sequence Context Sequence context of the change including 10 bases before
and 10 bases after the change.
CpG Whether or not this nucleotide is part of a CpG dinucleotide
(Yes/No).
Reference Reference number or resource name, SNP means the
NCBI dbSNP database.
Ref ID Identification number used by the source; the RefSNP
number is shown if the data is from the NCBI dbSNP
database.

 
 

References

1. Jennifer Couzin. Cancer Sharpshooters Rely on DNA Tests for a Better Aim. Science, 2004;305:1222-1223
 
2. Fukuoka, M., Yano, S., Giaccone, G., et al., Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer., J. Clin. Oncol.;21:2237-46, 2003.
 
3. Lynch et al., Activiating mutations in the Epidermal Growth Factor Receptor underlying responsiveness of Non-Small-Cell Lung Cancer to Gefitinib. NEJM, 2004;
350(21): 2129-2139.
 
4. Paez et al., EGFR mutations in lung cancer: correlation with clinical response to Gefitinib therapy. Science, 2004; 304: 1497-1500.
 
5. Pao, W. et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Published online in Proceedings of the National Academy of Sciences on August 23, 2004.
 
6. Personalized Medicine in Cancer: Matching Patients and Drugs. Genome News Network (http://www.genomenewsnetwork.org/articles/2004/10/28/matchingpatients.php)
 
7. Gazdar AF, et al., Mutations and addiction to EGFR:the Achilles ‘heal’ of lung cancers? Trends Mol Med. 2004 Oct;10(10):481-6.
 
8. Huang SF, et al., High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. Clin Cancer Res. 2004 Dec 15;10(24):8195-203.
 
9. Couzin J. Pharmacogenomics. Cancer sharpshooters rely on DNA tests for a better aim. Science. 2004 Aug 27;305(5688):1222-3
 
10. Sordella R, et al., Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science. 2004 Aug 20;305(5687):1163-7. Epub 2004 Jul 29.
 
11. Kosaka T, et al., Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res. 2004 Dec 15;64(24):8919-23.
 
12. Marchetti A, et al., EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol. 2005 Feb 1;23(4):857-65.
 
13. Tokumo M, et al., The Relationship between Epidermal Growth Factor Receptor Mutations and Clinicopathologic Features in Non-Small Cell Lung Cancers. Clin Cancer Res. 2005 Feb 1;11(3):1167-1173.
 
14. Han SW, et al., Predictive and Prognostic Impact of Epidermal Growth Factor Receptor Mutation in Non-Small-Cell Lung Cancer Patients Treated With Gefitinib. J Clin Oncol. 2005 Feb 14
 
15. Mitsudomi T, et al., Mutations of the Epidermal Growth Factor Receptor Gene Predict Prolonged Survival After Gefitinib Treatment in Patients with Non-Small-Cell Lung Cancer With Postoperative Recurrence J Clin Oncol. 2005 Feb 28
 
16. Shigematsu H, et al., Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers J Natl Cancer Inst. 2005 Mar 2;97(5):339-46
 
17. Kim KS, et al., Predictors of the response to gefitinib in refractory non-small cell lung cancer. Clin Cancer Res. 2005 Mar 15;11(6):2244-51.
 
19. Cappuzzo F, et al., Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst. 2005 May 4;97(9):643-55.
 
20. Cortes-Funes H, et al., Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients. Ann Oncol. 2005 Apr 25;
 
21. Soung YH, et al., Mutational analysis of EGFR and K-RAS genes in lung adenocarcinomas. Virchows Arch. 2005 Apr 7; [Epub ahead of print]
 
22. Sasaki H, et al., EGFR Mutation status in Japanese lung cancer patients: genotyping analysis using LightCycler. Clin Cancer Res. 2005 Apr 15;11(8):2924-9.
 
23. Chou TY, et al., Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer. Clin Cancer Res. 2005 May 15;11(10):3750-7.
 
24. Pao W, et al., Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2005 Mar;2(3):e73. Epub 2005 Feb 22.
 
25. Sasaki H, et al., EGFR and erbB2 mutation status in Japanese lung cancer patients. Int J Cancer. 2005 Jul 7
 
26. Eberhard DA, et al., Mutations in the Epidermal Growth Factor Receptor and in KRAS Are Predictive and Prognostic Indicators in Patients With Non-Small-Cell Lung Cancer Treated With Chemotherapy Alone and in Combination With Erlotinib. J Clin Oncol. 2005 Jul 25; [Epub ahead of print]
 
27. Takano T, et al., Epidermal Growth Factor Receptor Gene Mutations and Increased Copy Numbers Predict Gefitinib Sensitivity in Patients With Recurrent Non-Small-Cell Lung Cancer. J Clin Oncol. 2005 Jul 5
 
28. Tsao MS, et al., Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med. 2005 Jul 14;353(2):133-44.
 
29. Mu XL, et al., Gefitinib-sensitive mutations of the epidermal growth factor receptor tyrosine kinase domain in chinese patients with non-small cell lung cancer. Clin Cancer Res. 2005 Jun 15;11(12):4289-94.
 
30. Sonobe M, et al., Mutations in the epidermal growth factor receptor gene are linked to smoking-independent, lung adenocarcinoma. Br J Cancer. 2005 Jul 26; [Epub ahead of print]
 
31. Taron M, et al., Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. Clin Cancer Res. 2005 Aug 15;11(16):5878-85.
 
32. Mukohara T, et al., Differential effects of gefitinib and cetuximab on non-small-cell lung cancers bearing epidermal growth factor receptor mutations. J Natl Cancer Inst. 2005 Aug 17;97(16):1185-94.
 
33. Zhang XT, et al., The EGFR mutation and its correlation with response of gefitinib in previously treated Chinese patients with advanced non-small-cell lung cancer. Ann Oncol. 2005 Aug;16(8):1334-42. Epub 2005 Jun 14.
 
34. Ren GP, et al., Epidermal growth factor receptor mutations detected in tumors from Chinese "never smokers" with lung adenocarcinoma. Chin Med J (Engl). 2005 May 5;118(9):769-71.
 
35. Pan ZK, et al., Epidermal Growth Factor Receptor Mutation in Chinese Patients with Non-small Cell Lung Cancer Ai Zheng. 2005 Aug;24(8):919-23. Chinese.