title: A very low incidence of BRAF mutations in Middle Eastern colorectal carcinoma.
abstract: BACKGROUND
  Recent studies emphasize the role of BRAF as a genetic marker for prediction, prognosis and risk stratification in colorectal cancer. Earlier studies have reported the incidence of BRAF mutations in the range of 5-20% in colorectal carcinomas (CRC) and are predominantly seen in the serrated adenoma-carcinoma pathway characterized by microsatellite instability (MSI-H) and hypermethylation of the MLH1 gene in the setting of the CpG island methylator phenotype (CIMP). Due to the lack of data on the true incidence of BRAF mutations in Saudi Arabia, we sought to analyze the incidence of BRAF mutations in this ethnic group.
  
  
  METHODS
  770 CRC cases were analyzed for BRAF and KRAS mutations by direct DNA sequencing.
  
  
  RESULTS
  BRAF gene mutations were seen in 2.5% (19/757) CRC analyzed and BRAF V600E somatic mutation constituted 90% (17/19) of all BRAF mutations. BRAF mutations were significantly associated with right sided tumors (p = 0.0019), MSI-H status (p = 0.0144), CIMP (p = 0.0017) and a high proliferative index of Ki67 expression (p = 0.0162). Incidence of KRAS mutations was 28.6% (216/755) and a mutual exclusivity was noted with BRAF mutations (p = 0.0518; a trend was seen).
  
  
  CONCLUSIONS
  Our results highlight the low incidence of BRAF mutations and CIMP in CRC from Saudi Arabia. This could be attributed to ethnic differences and warrant further investigation to elucidate the effect of other environmental and genetic factors. These findings indirectly suggest the possibility of a higher incidence of familial hereditary colorectal cancers especially Hereditary non polyposis colorectal cancer (HNPCC) syndrome /Lynch Syndrome (LS) in Saudi Arabia.
authors.forename: Abdul K
authors.initials: AK
authors.lastname: Siraj
authors.forename: Rong
authors.initials: R
authors.lastname: Bu
authors.forename: Sarita
authors.initials: S
authors.lastname: Prabhakaran
authors.forename: Prashant
authors.initials: P
authors.lastname: Bavi
authors.forename: Shaham
authors.initials: S
authors.lastname: Beg
authors.forename: Mohsen
authors.initials: M
authors.lastname: Al Hazmi
authors.forename: Maha
authors.initials: M
authors.lastname: Al-Rasheed
authors.forename: Khadija
authors.initials: K
authors.lastname: Alobaisi
authors.forename: Fouad
authors.initials: F
authors.lastname: Al-Dayel
authors.forename: Hadeel
authors.initials: H
authors.lastname: AlManea
authors.forename: Nasser
authors.initials: N
authors.lastname: Al-Sanea
authors.forename: Shahab
authors.initials: S
authors.lastname: Uddin
authors.affiliation: Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P,O, Box 3354 Riyadh 11211, Saudi Arabia. kkuraya@kfshrc.edu.sa.
authors.forename: Khawla S
authors.initials: KS
authors.lastname: Al-Kuraya
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009687:Nuclear Proteins; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012529:Saudi Arabia
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1