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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

Palomba, Grazia and Colombino, Maria and Contu, Antonio and Massidda, Bruno and Baldino, Giovanni and Pazzola, Antonio and Ionta, Maria Teresa and Capelli, Francesca and Trova, Vittorio and Sedda, Tito and Sanna, Giovanni and Tanda, Francesco and Budroni, Mario and Palmieri, Giuseppe and Cossu, Antonio (2012) 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, Vol. 10 (178), p. 19. eISSN 1479-5876. Article.

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DOI: 10.1186/1479-5876-10-178

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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.

Item Type:Article
ID Code:8064
Status:Published
Refereed:Yes
Uncontrolled Keywords:Colorectal carcinoma, KRAS gene, BRAF gene, PIK3CA gene, mutation analysis, cancer genetic heterogeneity
Subjects:Area 06 - Scienze mediche > MED/08 Anatomia patologica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Chirurgiche, Microchirurgiche e Mediche
002 Altri enti e centri di ricerca del Nord Sardegna > Azienda ASL1, Sassari
001 Università di Sassari > 03 Istituti > Anatomia patologica
002 Altri enti e centri di ricerca del Nord Sardegna > Azienda ASL3, Nuoro
002 Altri enti e centri di ricerca del Nord Sardegna > CNR-Consiglio Nazionale delle Ricerche > Istituto di chimica biomolecolare, Sassari
002 Altri enti e centri di ricerca del Nord Sardegna > Azienda ASL5, Oristano
Publisher:BioMed Central
eISSN:1479-5876
Copyright Holders:© 2012 Palomba et al. ; licensee BioMed Central Ltd.
Deposited On:16 Oct 2012 10:41

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