Colorectal Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Feb 21, 2008; 14(7): 1053-1059
Published online Feb 21, 2008. doi: 10.3748/wjg.14.1053
Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-deficient colorectal cancers
Marie-Pierre Buisine, Agnès Wacrenier, Christophe Mariette, Emmanuelle Leteurtre, Fabienne Escande, Sana Aissi, Amandine Ketele, Annette Leclercq, Nicole Porchet, Thécla Lesuffleur
Marie-Pierre Buisine, Nicole Porchet, Centre de Recherche Jean-Pierre Aubert-JPARC, INSERM U837, Equipe Mucines, différenciation et cancérogenèse épithéliales, Laboratoire de Biochimie et Biologie Moléculaire, CHRU de Lille, and Faculté de Médecine H. Warembourg, Université de Lille 2, Lille, France
Agnès Wacrenier, Laboratoire d’Anatomie et Cytologie Pathologiques, CHRU de Lille, Lille, France
Emmanuelle Leteurtre, Centre de Recherche Jean-Pierre Aubert-JPARC, INSERM U837, Laboratoire d’Anatomie et Cytologie Pathologiques, CHRU de Lille, and Faculté de Médecine H. Warembourg, Université de Lille 2, Lille, France
Christophe Mariette, Centre de Recherche Jean-Pierre Aubert-JPARC, INSERM U837, Service de Chirurgie Digestive et Générale, CHRU de Lille, and Faculté de Médecine H. Warembourg, Université de Lille 2, Lille, France
Fabienne Escande, Centre de Recherche Jean-Pierre Aubert-JPARC, INSERM U837, and Laboratoire de Biochimie et Biologie Moléculaire, CHRU de Lille, Lille, France
Sana Aissi, Centre de Recherche Jean-Pierre Aubert-JPARC, INSERM U837, Laboratoire de Biochimie et Biologie Moléculaire, CHRU de Lille, Lille, France
Sana Aissi, Laboratoire d’Immunologie et Génétique, Tunis-El Manar, Tunisie
Amandine Ketele, Centre de Recherche Jean-Pierre Aubert- JPARC, INSERM U837, Lille, France
Annette Leclercq, Laboratoire de Biochimie et Biologie Moléculaire, CHRU de Lille, Lille, France
Thécla Lesuffleur, Centre de Recherche Jean-Pierre Aubert- JPARC, INSERM U837, Lille, France; present address INSERM U843, Université Paris 7, Hôpital R. Debré, Paris, France
Correspondence to: Marie-Pierre Buisine, Centre de Recherche Jean-Pierre Aubert, INSERM U837, place de Verdun, 59045 Lille cedex, France. buisine@lille.inserm.fr
Telephone: +33-3-20298850
Fax: +33-3-20538562
Received: April 18, 2007
Revised: September 5, 2007
Published online: February 21, 2008
Abstract

AIM: To investigate the polymorphic simple sequence repeat in intron 1 of the epidermal growth factor receptor gene (EGFR) (CA-SSRI), which is known to affect the efficiency of gene transcription as a putative target of the mismatch repair (MMR) machinery in colorectal tumors.

METHODS: The CA-SSR I genotype was analyzed in a total of 86 primary colorectal tumors, selected upon their microsatellite instability (MSI) status [42 with high frequency MSI (MSI-H) and 44 microsatellite stable (MSS)] and their respective normal tissue. The effect of the CA-SSR I genotype on the expression of the EGFR gene was evaluated in 18 specimens using quantitative real-time reverse transcription PCR and immunohistochemistry.

RESULTS: Mutations in CA-SSR I were detected in 86% (36 of 42) of MSI-H colorectal tumors and 0% (0 of 44) of MSS tumors, indicating the EGFR gene as a novel putative specific target of the defective MMR system (P < 0.001). Impaired expression of EGFR was detected in most of the colorectal tumors analyzed [6/12 (50%) at the mRNA level and 15/18 (83%) at the peptide level]. However, no association was apparent between EGFR expression and CA-SSR I status in tumors or normal tissues.

CONCLUSION: Our results suggest that CA-SSRI sequence does not contribute to the regulation of EGFR transcription in colon, and should thus not be considered as a promising predictive marker for response to EGFR inhibitors in patients with colorectal cancer.

Keywords: Epidermal growth factor receptor; Microsatellite instability; Allelic imbalance; Gene polymorphism; Expression; Colorectal cancer