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

Journal of Translational Medicine

Antonio Cossu⁹  Giuseppe Palmieri⁵  Mario Budroni⁶  Francesco Tanda⁷  Giovanni Sanna^1,10  Tito Sedda⁴  Vittorio Trova³  Francesca Capelli¹  MariaTeresa Ionta^1,11  Antonio Pazzola²  Giovanni Baldino²  Bruno Massidda^1,11  Antonio Contu²  Maria Colombino⁸  Grazia Palomba⁸ 

[1] Oncologia, ASL, Nuoro, Italy;Servizio Oncologia, ASL1, Sassari, Italy;Oncologia, ASL, Alghero, Italy;Oncologia, ASL, Oristano, Italy;Unit of Cancer Genetics, Institute Biomolecular Chemistry (ICB), National Research Council (CNR), Traversa La Crucca 3, Loc. Baldinca Li Punti, Sassari 07100, Italy;Servizio Epidemiologia, ASL1, Sassari, Italy;Anatomia Patologica, Università di Sassari, Sassari, Italy;Istituto di Chimica Biomolecolare, CNR, Sassari, Italy;Anatomia Patologica, AOU, Sassari, Italy;Oncologia Medica, AOU, Sassari, Italy;Oncologia Medica, Università di Cagliari, Cagliari, Italy

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

Others  :  1205903
DOI  :  10.1186/1479-5876-10-178

 received in 2012-05-11, accepted in 2012-08-23,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Palomba et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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