Abstract
Colorectal cancer (CRC) is usually diagnosed in the metastatic stage, when chemotherapy and molecularly-targeted therapies, instead of surgery, play the most important therapeutic role. Application of anti-epidermal growth factor receptor (EGFR) therapy requires the analysis of RAS mutation status and only RAS wild-type (wt) patients are qualified for the therapy. The objective of this study was to analyze driver mutations in KRAS, NRAS, BRAF, and PIK3CA genes in CRC patients. We assessed the KRAS, NRAS, BRAF, and PIK3CA genes in 102 inoperable, locally advanced and advanced CRC patients. Real-time polymerase chain reaction (RT-PCR) and high resolution melt PCR (HRM-PCR) techniques with DNA intercalating dye were applied in the study. Forty-six patients demonstrated the presence of examined mutations (45.1%). No significant differences in driver mutation occurrence between men and women, as well as between younger (<65 years) and older (≥65 years) patients were found. The mutations were present significantly more frequently in metastatic than in primary tumors (p = 0.039) due to the high incidence of KRAS gene mutations in metastatic tissue. BRAF and PIK3CA mutations were found only in primary tumors. The incidence of PIK3CA mutations was significantly higher (11.77%) in early than in advanced stages of the disease (1.96%; p = 0.05); NRAS mutations were found only in metastatic cancer (7.85%; p = 0.041). Only a single mutation of the PIK3CA and no mutations of NRAS were found in rectal cancer. Our results have shown low occurrence of driver mutations in Polish CRC patients, involving also mutations in rarely tested genes. The extent of the research panel of additional mutations could contribute to creating a better method of qualifying patients for molecularly targeted therapies and obtaining a better outcome for these therapeutic strategies.
Highlights
Colorectal cancer (CRC) is one of the leading causes of cancer death and one of the most common cancers among both men and women in developed countries
Application of anti-epidermal growth factor receptor (EGFR) therapy requires the analysis of RAS mutation status and only RAS wild-type patients are qualified for the therapy
Our results have shown low occurrence of driver mutations in Polish CRC patients, involving mutations in rarely tested genes
Summary
Colorectal cancer (CRC) is one of the leading causes of cancer death and one of the most common cancers among both men and women in developed countries. In many European countries, bevacizumab, cetuximab and panitumumab were the molecularly targeted drugs available for advanced CRC.[3] The first one is a monoclonal antibody directed against vascular endothelial growth factor (VEGF), which inhibits angiogenesis and leads to the increase of blood vessel pressure. Two other drugs are monoclonal antibodies against epidermal growth factor receptor (EGFR), and their mechanism of action involves blocking the proliferation signal of tumor cells by inhibiting the EGFR signaling pathway (EGFR/ Pi3K/AKT/mTOR or EGFR/RAS/RAF/MAPK/ERK).3 Application of these drugs requires an analysis of RAS gene mutations status and only patients with RAS wildtype (wt) are qualified for the therapy. Colorectal cancer (CRC) is usually diagnosed in the metastatic stage, when chemotherapy and molecularly-targeted therapies, instead of surgery, play the most important therapeutic role. Application of anti-epidermal growth factor receptor (EGFR) therapy requires the analysis of RAS mutation status and only RAS wild-type (wt) patients are qualified for the therapy
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