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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2012

Open Access 01-12-2012 | Research

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

Authors: Grazia Palomba, Maria Colombino, Antonio Contu, Bruno Massidda, Giovanni Baldino, Antonio Pazzola, MariaTeresa Ionta, Francesca Capelli, Vittorio Trova, Tito Sedda, Giovanni Sanna, Francesco Tanda, Mario Budroni, Giuseppe Palmieri, Antonio Cossu, Sardinian Translational Oncology Group (STOG)

Published in: Journal of Translational Medicine | Issue 1/2012

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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.
Appendix
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Metadata
Title
Prevalence of KRAS, BRAF, and PIK3CA somatic mutations in patients with colorectal carcinoma may vary in the same population: clues from Sardinia
Authors
Grazia Palomba
Maria Colombino
Antonio Contu
Bruno Massidda
Giovanni Baldino
Antonio Pazzola
MariaTeresa Ionta
Francesca Capelli
Vittorio Trova
Tito Sedda
Giovanni Sanna
Francesco Tanda
Mario Budroni
Giuseppe Palmieri
Antonio Cossu
Sardinian Translational Oncology Group (STOG)
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-10-178

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