Database of somatic mutations in EGFR with analyses revealing indel hotspots but no smoking-associated signature †
Dongqing Gu
Clinical Molecular Diagnostic Laboratory (CMDL), Department of Molecular Diagnosis, City of Hope National Medical Center, City of Hope, Duarte, California
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
Search for more papers by this authorWilliam A. Scaringe
Clinical Molecular Diagnostic Laboratory (CMDL), Department of Molecular Diagnosis, City of Hope National Medical Center, City of Hope, Duarte, California
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
Search for more papers by this authorKai Li
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
SNP Institute, Nanhua University, Hengyang, Hunan, China
Search for more papers by this authorJuan-Sebastian Saldivar
Clinical Molecular Diagnostic Laboratory (CMDL), Department of Molecular Diagnosis, City of Hope National Medical Center, City of Hope, Duarte, California
Search for more papers by this authorKathleen A. Hill
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
Department of Biology, The University of Western Ontario, London, Ontario, Canada
Search for more papers by this authorZhenbin Chen
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
Search for more papers by this authorKelly D. Gonzalez
Clinical Molecular Diagnostic Laboratory (CMDL), Department of Molecular Diagnosis, City of Hope National Medical Center, City of Hope, Duarte, California
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
Search for more papers by this authorCorresponding Author
Steve S. Sommer
Clinical Molecular Diagnostic Laboratory (CMDL), Department of Molecular Diagnosis, City of Hope National Medical Center, City of Hope, Duarte, California
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
Department of Molecular Genetics, Beckman Research Institute/City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-0269Search for more papers by this authorDongqing Gu
Clinical Molecular Diagnostic Laboratory (CMDL), Department of Molecular Diagnosis, City of Hope National Medical Center, City of Hope, Duarte, California
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
Search for more papers by this authorWilliam A. Scaringe
Clinical Molecular Diagnostic Laboratory (CMDL), Department of Molecular Diagnosis, City of Hope National Medical Center, City of Hope, Duarte, California
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
Search for more papers by this authorKai Li
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
SNP Institute, Nanhua University, Hengyang, Hunan, China
Search for more papers by this authorJuan-Sebastian Saldivar
Clinical Molecular Diagnostic Laboratory (CMDL), Department of Molecular Diagnosis, City of Hope National Medical Center, City of Hope, Duarte, California
Search for more papers by this authorKathleen A. Hill
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
Department of Biology, The University of Western Ontario, London, Ontario, Canada
Search for more papers by this authorZhenbin Chen
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
Search for more papers by this authorKelly D. Gonzalez
Clinical Molecular Diagnostic Laboratory (CMDL), Department of Molecular Diagnosis, City of Hope National Medical Center, City of Hope, Duarte, California
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
Search for more papers by this authorCorresponding Author
Steve S. Sommer
Clinical Molecular Diagnostic Laboratory (CMDL), Department of Molecular Diagnosis, City of Hope National Medical Center, City of Hope, Duarte, California
Department of Molecular Genetics, City of Hope National Medical Center, City of Hope, Duarte, California
Department of Molecular Genetics, Beckman Research Institute/City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-0269Search for more papers by this authorCommunicated by Marc Greenblatt
Abstract
We created an Epidermal Growth Factor Receptor (EGFR) Mutation Database (http://www.cityofhope.org/cmdl/egfr_db) that curates a convenient compilation of somatic EGFR mutations in non-small-cell lung cancer (NSCLC) and associated epidemiological and methodological data, including response to the tyrosine kinase inhibitors Gefitinib and Erlotinib. Herein, we analyze 809 mutations collected from 26 publications. Four super hotspots account for 70% of reported mutations while two-thirds of 131 unique mutations have been reported only once and account for only 11% of reported mutations. Consistent with strong biological selection for gain of function, the reported mutations are virtually all missense substitutions or in-frame microdeletions, microinsertions, or microindels (colocalized insertion and deletion with a net gain or loss of 1–50 nucleotides). Microdeletions and microindels are common in a region of exon 19. Microindels, which account for 8% of mutations, have smaller inserted sequences (95% are 1 to 5 bp) and are elevated 16-fold relative to mouse somatic microindels and to human germline microindels. Microdeletions/microindels are significantly more frequent in responders to Gefitinib or Erlotinib (P = 0.003). In addition, EGFR mutations in smokers do not carry signatures of mutagens in cigarette smoke. Otherwise, the mutation pattern does not differ significantly with respect to gender, age, or tumor histology. The EGFR Mutation Database is a central resource of EGFR sequence variant data for clinicians, geneticists, and other researchers. Authors are encouraged to submit new publications with EGFR sequence variants to be included in the database or to provide direct submissions via The WayStation submission and publication process (http://www.centralmutations.org). Hum Mutat 28(8), 760–770, 2007. © 2007 Wiley-Liss, Inc.
Supporting Information
The Supplementary Material referred to in this article can be accessed at http://www.interscience.wiley.com/jpages/1059–7794/suppmat .
| Filename | Description |
|---|---|
| jws-humu.20512.pdf118 KB | Supplementary Tables S1-S3, Supplementary Figures S1a-S1b |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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