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Open Access Research article

Genetic variations of the A13/A14 repeat located within the EGFR 3′ untranslated region have no oncogenic effect in patients with colorectal cancer

Nasrin Sarafan-Vasseur1, David Sefrioui12, David Tougeron3, Aude Lamy14, France Blanchard4, Florence Le Pessot5, Frédéric Di Fiore12, Pierre Michel12, Stéphane Bézieau6, Jean-Baptiste Latouche1, Thierry Frebourg1 and Richard Sesboüé1*

Author Affiliations

1 Inserm U1079, Institute for Biomedical Research and Innovation, University of Rouen, 22 Boulevard Gambetta, CS 76183, Rouen Cedex, 76183, France

2 Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, 1 Rue de Germont, Rouen Cedex, 76031, France

3 Department of Gastroenterology and Department of Oncology, Poitiers University Hospital, Laboratoire Inflammation Tissus Epithéliaux et Cytokines, University of Poitiers, Poitiers, EA 4331, France

4 Laboratory of Tumor Genetics, University Hospital, 1 Rue de Germont, Rouen Cedex, 76031, France

5 Department of Pathology, University Hospital, 1 Rue de Germont, Rouen Cedex, 76031, France

6 Department of Genetics, Nantes University Hospital, Nantes, France

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BMC Cancer 2013, 13:183  doi:10.1186/1471-2407-13-183

Published: 8 April 2013

Abstract

Background

The EGFR 3′ untranslated region (UTR) harbors a polyadenine repeat which is polymorphic (A13/A14) and undergoes somatic deletions in microsatellite instability (MSI) colorectal cancer (CRC). These mutations could be oncogenic in colorectal tissue since they were shown to result into increased EGFR mRNA stability in CRC cell lines.

Methods

First, we determined in a case control study including 429 CRC patients corresponding to different groups selected or not on age of tumor onset and/or familial history and/or MSI, whether or not, the germline EGFR A13/A14 polymorphism constitutes a genetic risk factor for CRC; second, we investigated the frequency of somatic mutations of this repeat in 179 CRC and their impact on EGFR expression.

Results

No statistically significant difference in allelic frequencies of the EGFR polyA repeat polymorphism was observed between CRC patients and controls. Somatic mutations affecting the EGFR 3′UTR polyA tract were detected in 47/80 (58.8%) MSI CRC versus 0/99 microsatellite stable (MSS) tumors. Comparative analysis in 21 CRC samples of EGFR expression, between tumor and non malignant tissues, using two independent methods showed that somatic mutations of the EGFR polyA repeat did not result into an EGFR mRNA increase.

Conclusion

Germline and somatic genetic variations occurring within the EGFR 3′ UTR polyA tract have no impact on CRC genetic risk and EGFR expression, respectively. Genotyping of the EGFR polyA tract has no clinical utility to identify patients with a high risk for CRC or patients who could benefit from anti-EGFR antibodies.

Keywords:
Colorectal cancer; EGFR; Polymorphism; Microsatellite instability; Targeted therapy