title: Relationship between expression of ras p21 oncoprotein and mutation status of the K-ras gene in sporadic colorectal cancer patients in Tunisia.
abstract: BACKGROUND
  The K-ras proto-oncogene encodes a protein (p21-ras) belonging to the family of GTP/GDP-binding proteins with GTPase activity. The activation of ras family genes plays an important role in colorectal tumorigenesis. Frequency of K-ras mutations and overexpression of the protein in colorectal cancer (CRC) vary between 14% and 50% and between 29% and 76%, respectively.
  
  
  OBJECTIVE
  We investigated the clinicopathologic characteristics of patients with CRC and their relationship with point mutations of K-ras oncogene codons 12/13 and ras p21 expression.
  
  
  METHODS
  K-ras codons 12 and 13 point mutations were examined by direct sequence analysis, whereas the ras p21 expression was evaluated using immunohistochemistry.
  
  
  RESULTS
  Statistical analysis of immunohistochemical results showed that the expression of ras p21 was correlated with the advanced age of patients (P=0.0001), whereas loss of signal was associated with mucinous histotype (P=0.0001). Mutations in the K-ras gene were detected in 12 of the patients with CRC. Mutations in K-ras gene were found in 12 of 52 tumors (23.07%), and 7 mutations were G→A transitions (58.33% of all mutations), 4 were G→T transversions (33.33%), and only 1 was G→C transversion (8.33%). A total of 83.33% of the mutation occurred at codon 12 and 16.67% at codon 13. Moreover, K-ras mutations were associated with the sex of patients (P=0.017).
  
  
  CONCLUSIONS
  Genetic K-ras alterations were rather low in the Tunisian population, but further study is necessary to unravel the molecular background of CRC.
authors.affiliation: Laboratory of Colorectal Cancer Research UR03ES04, Science University Tunis, Tunisia. soraya.s02@hotmail.fr
authors.forename: Souraya
authors.initials: S
authors.lastname: Sammoud
authors.forename: Meriem
authors.initials: M
authors.lastname: Khiari
authors.forename: Amara
authors.initials: A
authors.lastname: Semeh
authors.forename: Lounis
authors.initials: L
authors.lastname: Amine
authors.forename: Chaar
authors.initials: C
authors.lastname: Ines
authors.forename: Arfaoui
authors.initials: A
authors.lastname: Amira
authors.forename: Kriaa
authors.initials: K
authors.lastname: Lilia
authors.forename: Khalfallah
authors.initials: K
authors.lastname: Taher
authors.forename: Mzabi
authors.initials: M
authors.lastname: Sabeh
authors.forename: Bouraoui
authors.initials: B
authors.lastname: Saadia
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis / Q000235:genetics; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D012189:Retrospective Studies; D014416:Tunisia
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D015689:Oncogene Protein p21(ras)