Epidermal growth factor receptor structural alterations in gastric cancer

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.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.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.Gastric cancer remains the second leading cause of cancer death worldwide [1] a scenario that highlights the need for more specific and efficient therapies. The exact mechanisms underlying gastric carcinogenesis are not yet fully understood, but evidence points to an association with pathways involved in developmental processes [2]. Key molecules of these pathways are the receptor tyrosine kinases (RTKs), which are found to be aberrantly activated or overexpressed in a variety of tumours and therefore represent promising targets for therapeutical intervention.The members of the RTK superfamily of ERBB receptors are glycoproteins that consist of an extracellular domain where the binding of ligands takes place, a short lipophilic transmembrane domain, and an intracellular domain carrying the tyrosine kinase activity [3,4]. They are expressed in several tissues of epithelial, mesenchymal and neuronal origin, where they play pivotal r