title: Prevalence of mutations in APC, CTNNB1, and BRAF in Tunisian patients with sporadic colorectal cancer.
abstract: Sporadic colorectal tumorigenesis is caused by alterations in the Wnt (APC, CTNNB1) and Ras pathways. Our objective was to analyze the occurrence of these genetic alterations in relation to tumor and patient characteristics. The prevalence of somatic alteration in the hot-spot regions of the APC, BRAF, and CTNNB1 genes was investigated in 48 unselected and unrelated Tunisian patients with sporadic colorectal cancer, and the association between the molecular features at these genes in relation to tumor and patient characteristics (age at diagnosis, sex, tumor localization, stage, and differentiation) was analyzed. Loss of heterozygosity was observed at the APC locus in 52% of the analyzed tumors. 6 novel mutations were detected by polymerase chain reaction sequencing in the mutation cluster region of the APC gene. No mutations were observed in the CTNNB1 gene in any tumor, but 8% of tumors harbored mutation in the BRAF gene. Clinicopathological analyses showed an association between APC point mutations and the earliest occurrence of sporadic colorectal cancer. The findings confirm the heterogeneity of APC gene alteration and also reveal a particular profile of this pathology among Tunisian patients that confirms the epidemiological data for this country.
authors.affiliation: Laboratory of Human Genetics, Immunology, and Pathology, Faculty of Sciences-Tunis, University of Tunis, Campus Universitaire, El Manar I, Tunis 2092, Tunisia. karim.bougatef@fst.rnu.tn
authors.forename: Karim
authors.initials: K
authors.lastname: Bougatef
authors.forename: Slah
authors.initials: S
authors.lastname: Ouerhani
authors.forename: Amel
authors.initials: A
authors.lastname: Moussa
authors.forename: Nadia
authors.initials: N
authors.lastname: Kourda
authors.forename: Florence
authors.initials: F
authors.lastname: Coulet
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Colas
authors.forename: Yannick Blondeau
authors.initials: YB
authors.lastname: Lahely
authors.forename: Tawfik
authors.initials: T
authors.lastname: Najjar
authors.forename: Sarra
authors.initials: S
authors.lastname: Ben Jilani
authors.forename: Amel
authors.initials: A
authors.lastname: Benammar-Elgaaied
authors.forename: Florent
authors.initials: F
authors.lastname: Soubrier
authors.forename: Raja
authors.initials: R
authors.lastname: Marrakchi
mesh_terms: D017668:Age of Onset; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005260:Female; D005784:Gene Amplification; D017491:Genes, APC; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D014416:Tunisia; D051176:beta Catenin / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; D017931:DNA Primers; D004273:DNA, Neoplasm; D051176:beta Catenin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf