Liječnički vjesnik, Vol. 133 No. 11-12, 2011.
Pregledni rad
THE ROLE OF KRAS GENE MUTATION TESTING IN COLORECTAL CANCER – A PREDICTIVE BIOMARKER OF RESPONSE TO EGFR INHIBITORS THERAPY
Ivana Rako
Jasminka Jakić-Razumović
Domagoj Caban
Jadranka Sertić
Darko Katalinić
Hilda Golem
Stjepko Pleština
Sažetak
Activation of KRAS oncogene has been implicated in colorectal carcinogenesis. KRAS mutations can be detected in more than 30% of all patients with colorectal cancer (CRC). Most recently, regimens that include anti-epidermal growth factor receptor (EGFR) targeted antibodies, cetuximab and panitumumab, for metastatic CRC have been developed. Several recent studies have shown that patients with KRAS mutations in codons 12 and 13 in metastatic CRC do not benefit from anti-EGFR therapy. With the aim to determine KRAS status as predictive biomarker, 7 known mutations of KRAS gene in codons 12 or 13 on 44 CRC samples were tested. After DNA extraction from paraffin-embedded tumor tissue blocks, KRAS mutations were analysed using quantitative real-time PCR with internationally certified method, for the first time in Croatia. Mutations were detected in 12 tumor samples: five patients with Gly12Val (GGT>GTT), three with Gly12Asp (GGT>GAT), two patients with Gly13Asp (GGC>GAC), one patient with Gly12Ser (GGT>AGT) and one with Gly12Cys (GGT>TGT) mutation in tumor. Our data about KRAS mutational status in the sample of Croatian population diagnosed with CRC have shown that incidence of KRAS mutation is 27%, which is consistent with results already reported worldwide. The final result must be a proper selection of the correct therapy with EGFR inhibitors for the patients with CRC which is critical for improving clinical outcomes, unnecessary toxicities, side effects and financial cost.
Ključne riječi
: Colorectal neoplasms – genetics, pathology, drug therapy; Receptor, epidermal growth factor – genetics, metabolism, antagonists and inhibitors; Tumor markers, biological – metabolism; Ras proteins – genetics; Mutation – genetics; Proto-oncogene proteins – genetics; Drug resistance, neoplasm – genetics; Antibodies, monoclonal – therapeutic use
Hrčak ID:
171905
URI
Datum izdavanja:
29.12.2011.
Posjeta: 8.699 *