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Epidermal growth factor receptor structural alterations in gastric cancer

BACKGROUND: EGFR overexpression has been described in many human tumours including gastric cancer. In NSCLC patients somatic EGFR mutations, within the kinase domain of the protein, as well as gene amplification were associated with a good clinical response to EGFR inhibitors. In gastric tumours dat...

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Autores principales: Moutinho, Cátia, Mateus, Ana R, Milanezi, Fernanda, Carneiro, Fátima, Seruca, Raquel, Suriano, Gianpaolo
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2244615/
https://www.ncbi.nlm.nih.gov/pubmed/18199332
http://dx.doi.org/10.1186/1471-2407-8-10
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author Moutinho, Cátia
Mateus, Ana R
Milanezi, Fernanda
Carneiro, Fátima
Seruca, Raquel
Suriano, Gianpaolo
author_facet Moutinho, Cátia
Mateus, Ana R
Milanezi, Fernanda
Carneiro, Fátima
Seruca, Raquel
Suriano, Gianpaolo
author_sort Moutinho, Cátia
collection PubMed
description BACKGROUND: EGFR overexpression has been described in many human tumours including gastric cancer. In NSCLC patients somatic EGFR mutations, within the kinase domain of the protein, as well as gene amplification were associated with a good clinical response to EGFR inhibitors. In gastric tumours data concerning structural alterations of EGFR remains controversial. Given its possible therapeutic relevance, we aimed to determine the frequency and type of structural alterations of the EGFR gene in a series of primary gastric carcinomas. METHODS: Direct sequencing of the kinase domain of the EGFR gene was performed in a series of 77 primary gastric carcinomas. FISH analysis was performed in 30 cases. Association studies between EGFR alterations and the clinical pathological features of the tumours were performed. RESULTS: Within the 77 primary gastric carcinomas we found two EGFR somatic mutations and several EGFR polymorphisms in exon 20. Six different intronic sequence variants of EGFR were also found. Four gastric carcinomas showed balanced polysomy or EGFR gene amplification. We verified that gastric carcinoma with alterations of EGFR (somatic mutations or copy number variation) showed a significant increase of tumour size (p = 0.0094) in comparison to wild-type EGFR carcinomas. CONCLUSION: We demonstrate that EGFR structural alterations are rare in gastric carcinoma, but whenever present, it leads to tumour growth. We considered that searching for EGFR alterations in gastric cancer is likely to be clinically important in order to identify patients susceptible to respond to tyrosine kinase inhibitors.
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spelling pubmed-22446152008-02-15 Epidermal growth factor receptor structural alterations in gastric cancer Moutinho, Cátia Mateus, Ana R Milanezi, Fernanda Carneiro, Fátima Seruca, Raquel Suriano, Gianpaolo BMC Cancer Research Article BACKGROUND: EGFR overexpression has been described in many human tumours including gastric cancer. In NSCLC patients somatic EGFR mutations, within the kinase domain of the protein, as well as gene amplification were associated with a good clinical response to EGFR inhibitors. In gastric tumours data concerning structural alterations of EGFR remains controversial. Given its possible therapeutic relevance, we aimed to determine the frequency and type of structural alterations of the EGFR gene in a series of primary gastric carcinomas. METHODS: Direct sequencing of the kinase domain of the EGFR gene was performed in a series of 77 primary gastric carcinomas. FISH analysis was performed in 30 cases. Association studies between EGFR alterations and the clinical pathological features of the tumours were performed. RESULTS: Within the 77 primary gastric carcinomas we found two EGFR somatic mutations and several EGFR polymorphisms in exon 20. Six different intronic sequence variants of EGFR were also found. Four gastric carcinomas showed balanced polysomy or EGFR gene amplification. We verified that gastric carcinoma with alterations of EGFR (somatic mutations or copy number variation) showed a significant increase of tumour size (p = 0.0094) in comparison to wild-type EGFR carcinomas. CONCLUSION: We demonstrate that EGFR structural alterations are rare in gastric carcinoma, but whenever present, it leads to tumour growth. We considered that searching for EGFR alterations in gastric cancer is likely to be clinically important in order to identify patients susceptible to respond to tyrosine kinase inhibitors. BioMed Central 2008-01-16 /pmc/articles/PMC2244615/ /pubmed/18199332 http://dx.doi.org/10.1186/1471-2407-8-10 Text en Copyright © 2008 Moutinho et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Moutinho, Cátia
Mateus, Ana R
Milanezi, Fernanda
Carneiro, Fátima
Seruca, Raquel
Suriano, Gianpaolo
Epidermal growth factor receptor structural alterations in gastric cancer
title Epidermal growth factor receptor structural alterations in gastric cancer
title_full Epidermal growth factor receptor structural alterations in gastric cancer
title_fullStr Epidermal growth factor receptor structural alterations in gastric cancer
title_full_unstemmed Epidermal growth factor receptor structural alterations in gastric cancer
title_short Epidermal growth factor receptor structural alterations in gastric cancer
title_sort epidermal growth factor receptor structural alterations in gastric cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2244615/
https://www.ncbi.nlm.nih.gov/pubmed/18199332
http://dx.doi.org/10.1186/1471-2407-8-10
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