Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 1, January, p. 67–73

doi: 10.17219/acem/76162

Publication type: original article

Language: English

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

Kamila Wojas-Krawczyk1,A,C,D,E,F, Ewa Kalinka-Warzocha2,A,C,D,E,F, Katarzyna Reszka3,B,C,D, Marcin Nicoś1,B,C, Justyna Szumiło4,B,C,D, Sławomir Mańdziuk5,B,C, Katarzyna Szczepaniak6,C,D, Dorota Kupnicka7,B,C, Remigiusz Lewandowski8,B,C, Janusz Milanowski1,A,D,E,F, Paweł Krawczyk1,A,D,E,F

1 Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Poland

2 Polish Mother's Memorial Hospital Research Institute, Łódź, Poland

3 Genetic and Immunology Institute GENIM Ltd., Lublin, Poland

4 Department of Clinical Patomorphology, Medical University of Lublin, Poland

5 Oncology and Chemotherapy Unit, Medical University of Lublin, Poland

6 Chemotherapy Department, Regional Centre of Oncology, Nicolaus Copernicus Provincial Specialist Hospital, Łódź, Poland

7 Pathology Laboratory Synevo, Łódź, Poland

8 MolGenDia Ltd., Bydgoszcz, Poland

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.
Conclusion. 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.

Key words

colorectal cancer, PIK3CA, BRAF, molecularly targeted therapy, RAS mutation

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