RT Journal Article
SR Electronic
T1 <em>KRAS</em>, <em>NRAS</em> and <em>BRAF</em> mutations in Greek and Romanian patients with colorectal cancer: a cohort study
JF BMJ Open
JO BMJ Open
FD British Medical Journal Publishing Group
SP e004652
DO 10.1136/bmjopen-2013-004652
VO 4
IS 5
A1 Serban Negru
A1 Eirini Papadopoulou
A1 Angela Apessos
A1 Dana Lucia Stanculeanu
A1 Eliade Ciuleanu
A1 Constantin Volovat
A1 Adina Croitoru
A1 Stylianos Kakolyris
A1 Gerasimos Aravantinos
A1 Nikolaos Ziras
A1 Elias Athanasiadis
A1 Nikolaos Touroutoglou
A1 Nikolaos Pavlidis
A1 Haralabos P Kalofonos
A1 George Nasioulas
YR 2014
UL http://bmjopen.bmj.com/content/4/5/e004652.abstract
AB Objectives Treatment decision-making in colorectal cancer is often guided by tumour tissue molecular analysis. The aim of this study was the development and validation of a high-resolution melting (HRM) method for the detection of KRAS, NRAS and BRAF mutations in Greek and Romanian patients with colorectal cancer and determination of the frequency of these mutations in the respective populations. Setting Diagnostic molecular laboratory located in Athens, Greece. Participants 2425 patients with colorectal cancer participated in the study. Primary and secondary outcome measures 2071 patients with colorectal cancer (1699 of Greek and 372 of Romanian origin) were analysed for KRAS exon 2 mutations. In addition, 354 tumours from consecutive patients (196 Greek and 161 Romanian) were subjected to full KRAS (exons 2, 3 and 4), NRAS (exons 2, 3 and 4) and BRAF (exon 15) analysis. KRAS, NRAS and BRAF mutation detection was performed by a newly designed HRM analysis protocol, followed by Sanger sequencing. Results KRAS exon 2 mutations (codons 12/13) were detected in 702 of the 1699 Greek patients with colorectal carcinoma analysed (41.3%) and in 39.2% (146/372) of the Romanian patients. Among the 354 patients who were subjected to full KRAS, NRAS and BRAF analysis, 40.96% had KRAS exon 2 mutations (codons 12/13). Among the KRAS exon 2 wild-type patients 15.31% harboured additional RAS mutations and 12.44% BRAF mutations. The newly designed HRM method used showed a higher sensitivity compared with the sequencing method. Conclusions The HRM method developed was shown to be a reliable method for KRAS, NRAS and BRAF mutation detection. Furthermore, no difference in the mutation frequency of KRAS, NRAS and BRAF was observed between Greek and Romanian patients with colorectal cancer.