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Prevalence of KRAS, BRAF, and PIK3CA somatic mutations in patients with colorectal carcinoma may vary in the same population: clues from Sardinia

Grazia Palomba1, Maria Colombino1, Antonio Contu2, Bruno Massidda3, Giovanni Baldino2, Antonio Pazzola2, MariaTeresa Ionta3, Francesca Capelli4, Vittorio Trova5, Tito Sedda6, Giovanni Sanna7, Francesco Tanda8, Mario Budroni9, Sardinian Translational Oncology Group (STOG), Giuseppe Palmieri111* and Antonio Cossu10

Author Affiliations

1 Istituto di Chimica Biomolecolare, CNR, Sassari, Italy

2 Servizio Oncologia, ASL1, Sassari, Italy

3 Oncologia Medica, Università di Cagliari, Cagliari, Italy

4 Oncologia, ASL, Nuoro, Italy

5 Oncologia, ASL, Alghero, Italy

6 Oncologia, ASL, Oristano, Italy

7 Oncologia Medica, AOU, Sassari, Italy

8 Anatomia Patologica, Università di Sassari, Sassari, Italy

9 Servizio Epidemiologia, ASL1, Sassari, Italy

10 Anatomia Patologica, AOU, Sassari, Italy

11 Unit of Cancer Genetics, Institute Biomolecular Chemistry (ICB), National Research Council (CNR), Traversa La Crucca 3, Loc. Baldinca Li Punti, Sassari 07100, Italy

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Journal of Translational Medicine 2012, 10:178  doi:10.1186/1479-5876-10-178

Published: 29 August 2012



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.


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.


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.


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.

Colorectal carcinoma; KRAS gene; BRAF gene; PIK3CA gene; Mutation analysis; Cancer genetic heterogeneity