Analysis of KRAS, NRAS, BRAF, and PIK3CA mutations could predict metastases in colorectal cancer: A preliminary study

Abstract

Background. 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. Objectives. The objective of this study was to analyze driver mutations in KRAS, NRAS, BRAF, and PIK3CA genes in CRC patients. Material and methods. 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. Results. 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. Conclusions. 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.

Characterization of early recurrences following liver resection by ALPPS and two stage hepatectomy in patients with colorectal liver-metastases and small future liver remnants; a translational substudy of the LIGRO-RCT

“…This is somewhat higher than in the present study but is in line with the fact that all of the final 24 patients in our study group had undergone a macroscopically radical resection. 22 RAS mutations (KRAS or NRAS) have been linked to higher rates of positive resection margins as well as extrahepatic disease. 23,24 In the current study, only patients deemed tumor free after the final liver resection (e.g.…”

Current Perspectives on Circulating Tumor DNA, Precision Medicine, and Personalized Clinical Management of Cancer

“…In metastatic colorectal cancer, clinical use of anti-EGFR mAbs exhibits increased treatment efficiency. However, anti-EGFR therapies have shown efficiency in KRAS wild-type tumors cells subpopulations (79).…”

Analysis of KRAS, NRAS, and BRAF Mutations, Microsatellite Instability, and Relevant Prognosis Effects in Patients With Early Colorectal Cancer: A Cohort Study in East Asia

“…KRAS is located on human chromosome 12 and encodes a 21-kDa RAS protein that contains two subtypes, namely, KRAS4A and KRAS4B (12). Previous studies have shown that the mutation rate of KRAS in patients with CRC is 37%-56%, and the mutation status is related to tumor size, tumor location, degree of tumor differentiation, lymph node metastasis, and other factors (13)(14)(15)(16). Sideris (17) et al showed that KRAS mutation status may affect the prognosis of ECRC, as this is linked to distant recurrence.…”