title: Prevalence of KRAS, BRAF, and PIK3CA somatic mutations in patients with colorectal carcinoma may vary in the same population: clues from Sardinia.
abstract: BACKGROUND
  Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been recently investigated worldwide. In this population-based study, we evaluated the incidence rates and distribution of such somatic mutations in genetically isolated population from Sardinia.
  
  
  METHODS
  From April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (N = 478) were prospectively collected from Sardinian CRC patients at clinics across the entire island. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing.
  
  
  RESULTS
  Overall, KRAS tumour mutation rate was 30% (145/478 positive cases). Distribution of mutation carriers was surprisingly different within the island: 87/204 (43%) in North Sardinia vs. 58/274 (21%) in Middle-South Sardinia (p<0.001). Among 384 CRC cases whose DNA was available, only one (0.3%) patient carried a mutation in BRAF gene; PIK3CA was found mutated in 67 (17%) patients. A significant inverse distribution of PIK3CA mutation rates was observed within Sardinian population: 19/183 (10%) cases from northern vs. 48/201 (24%) cases from central-southern island (p<0.001). This heterogeneity in frequencies of KRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population. Preliminary clinical evaluation of 118 KRAS wild-type patients undergoing anti-EGFR-based treatment indicated lack of role for PIK3CA in predicting response to therapy.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that differences in patients' origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in candidate cancer genes.
authors.affiliation: Istituto di Chimica Biomolecolare, CNR, Sassari, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Palomba
authors.forename: Maria
authors.initials: M
authors.lastname: Colombino
authors.forename: Antonio
authors.initials: A
authors.lastname: Contu
authors.forename: Bruno
authors.initials: B
authors.lastname: Massidda
authors.forename: Giovanni
authors.initials: G
authors.lastname: Baldino
authors.forename: Antonio
authors.initials: A
authors.lastname: Pazzola
authors.forename: MariaTeresa
authors.initials: M
authors.lastname: Ionta
authors.forename: Francesca
authors.initials: F
authors.lastname: Capelli
authors.forename: Vittorio
authors.initials: V
authors.lastname: Trova
authors.forename: Tito
authors.initials: T
authors.lastname: Sedda
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sanna
authors.forename: Francesco
authors.initials: F
authors.lastname: Tanda
authors.forename: Mario
authors.initials: M
authors.lastname: Budroni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.forename: Marta
authors.initials: M
authors.lastname: Contu
authors.forename: Angelo
authors.initials: A
authors.lastname: Cuccu
authors.forename: Antonio
authors.initials: A
authors.lastname: Farris
authors.forename: Antonio
authors.initials: A
authors.lastname: Macciò
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mameli
authors.forename: Nina
authors.initials: N
authors.lastname: Olmeo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ortu
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Petretto
authors.forename: Valeria
authors.initials: V
authors.lastname: Pusceddu
authors.forename: Luciano
authors.initials: L
authors.lastname: Virdis
mesh_terms: D001483:Base Sequence; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D011905:Genes, ras; D005828:Genetics, Population; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: D017931:DNA Primers; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf