Annals of Oncology Advance Access published online on July 15, 2008
Annals of Oncology, doi:10.1093/annonc/mdn416
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Epidermal growth factor receptor (EGFR) status and K-Ras mutations in colorectal cancer
1 Centre Antoine-Lacassagne, Nice
2 Hôpital la Timone, Marseille
3 Hôpital la Pitié-Salpétrière, Paris
4 Hôpital l'Archet, Nice
5 CHU de Grenoble, Grenoble
6 Hôpital Tenon, Paris
7 Centre Hospitalier Lyon-Sud, Lyon
8 Institut Paoli-Calmettes, Marseille, France
* Correspondence to: Oncopharmacology Unit, EA3836, Centre Antoine Lacassagne, 33, Avenue de Valombrose, 06189 Nice Cedex 2, France. Tel: +33-4-92-03-15-53; Fax: +33-4-93-81-71-31; E-mail: gerard.milano{at}nice.fnclcc.fr
Background: In advanced colorectal cancer, K-Ras somatic mutations predict resistance to mAbs targeting epidermal growth factor receptor (EGFR). Relationships between K-Ras mutations and EGFR status have not been examined so far. We analyzed relationships between K-Ras mutations and EGFR tumoral status based on EGFR germinal polymorphisms, gene copy number and expression.
Methods: Eighty colorectal tumors (stage 0–IV) and 39 normal mucosas were analyzed. K-Ras mutations at codons 12 and 13 were detected by a sensitive enrichment double PCR–restriction fragment length polymorphism (RFLP) assay. EGFR gene polymorphisms at positions –216G>T, –191C>A and 497Arg>Lys were analyzed (PCR–RFLP), along with CA repeat polymorphism in intron 1 (fluorescent genotyping) and EGFR gene copy number (PCR amplification). EGFR expression was quantified by Scatchard binding assay.
Results: The number of EGFR high-affinity sites, dissociation constant (Kd), gene copy number, intron 1, –216G>T, –191C>A or 497Lys>Arg genotypes was not different between K-Ras-mutated or K-Ras-non-mutated tumors. No relationship was observed between any of the analyzed EGFR genotypes and EGFR expression. EGFR expression was not related to gene copy number. EGFR gene copy number in tumor and normal tissue was not correlated. The mean value of the tumor/normal mucosa gene copy number ratio was 1.16.
Conclusions: Present data clearly show that EGFR status is independent of K-Ras mutations in colorectal tumors.
EGFR, K-Ras mutations, colorectal cancer, scatchard assay, gene polymorphism, gene copy number
Received for publication April 7, 2008. Revision received June 2, 2008. Accepted for publication June 6, 2008.
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