Exon 19 of EGFR mutation in relation to the CA-repeat polymorphism in intron 1

Cancer Science
Naoko Sueoka-AraganeEisaburo Sueoka

Abstract

Epidermal growth factor receptor (EGFR) mutations in lung cancer enhance tyrosine kinase activity and increase sensitivity to the EGFR tyrosine kinase inhibitor, gefitinib. Mutation analysis of the EGFR gene is therefore indispensable for predicting gefitinib response. We investigated a CA-repeat polymorphism in the EGFR gene related to EGFR mutations. Because an increasing number of CA-repeats at intron 1 of the EGFR gene has been reported to reduce transcription activity, we examined the relationship between EGFR mutations and this CA-repeat polymorphism. EGFR mutations at exon 19 were closely associated with shorter CA-repeat length in the shorter allele, but this was not the case for EGFR mutations at exons 18 or 21. Increased intrinsic EGFR mRNA expression in non-cancerous lung tissues from lung adenocarcinoma patients was also significantly associated with shorter CA-repeat length. A higher frequency of EGFR mutations at exon 19 was associated with shorter CA-repeat length only in patients with high levels of EGFR mRNA expression. To determine the phenotypes of cells possessing shorter CA-repeats, an in vitro study using human bronchial epithelial cells with different CA-repeat lengths was performed; more rapid cell growt...Continue Reading

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Citations

Mar 5, 2013·Genetics Research·Salima Belguith-MaalejHassen Hadj Kacem
Jul 16, 2014·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Anne Winther LarsenBoe Sandahl Sorensen
Sep 17, 2009·Journal of Cancer Research and Clinical Oncology·Kazutoshi KomiyaEisaburo Sueoka
Jun 16, 2010·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Hidetaka UramotoKosei Yasumoto
Sep 21, 2015·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Anne Winther-LarsenPeter Meldgaard
Mar 24, 2009·Molecular Carcinogenesis·Albino Bacolla, Robert D Wells
Aug 10, 2013·Gynecologic Oncology·Duanduan MaJanet S Rader
Jan 1, 2011·Cancers·Melissa Oliveira-CunhaAjith K Siriwardena

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