title: Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-deficient colorectal cancers.
abstract: OBJECTIVE
  To investigate the polymorphic simple sequence repeat in intron 1 of the epidermal growth factor receptor gene (EGFR) (CA-SSR I), 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.
  
  
  CONCLUSIONS
  Our results suggest that CA-SSR I 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.
authors.affiliation: Centre de Recherche Jean-Pierre Aubert, INSERM U837, place de Verdun, 59045 Lille cedex, France. buisine@lille.inserm.fr
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Buisine
authors.forename: Agnes
authors.initials: A
authors.lastname: Wacrenier
authors.forename: Christophe
authors.initials: C
authors.lastname: Mariette
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leteurtre
authors.forename: Fabienne
authors.initials: F
authors.lastname: Escande
authors.forename: Sana
authors.initials: S
authors.lastname: Aissi
authors.forename: Amandine
authors.initials: A
authors.lastname: Ketele
authors.forename: Annette
authors.initials: A
authors.lastname: Leclercq
authors.forename: Nicole
authors.initials: N
authors.lastname: Porchet
authors.forename: Thecla
authors.initials: T
authors.lastname: Lesuffleur
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D053843:DNA Mismatch Repair; D018900:Dinucleotide Repeats; D018773:Genes, erbB-1; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007438:Introns; D018598:Minisatellite Repeats; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm