The Mutation Profiles of K-RAS/N-RAS Genes in Metastatic Colorectal Cancer Patients

Abstract

Objective: RAS genes are members of the RAS/Mitogen activated protein kinase pathway which is induced by Epidermal Growth Factor Receptor (EGFR). Mutations in genes in this pathway trigger cancer development. In colorectal cancer, mutations in RAS genes cause resistance to EGRF- targeted therapy. In the treatment of metastatic colorectal cancer, EGFR’s monoclonal antibodies are widely used as chemotherapeutic agents. Kirsten-RAS mutations are found in 30-50% and N-RAS mutations are found in 2-3% of colorectal cancer. In this study, we aimed to analyze Kirsten-RAS /N-RAS mutations in patients with metastatic colorectal cancer. Methods: One hundred of metastatic colorectal cancer patients resistant to EGFR- targeted therapy were scanned for the Kirsten-RAS mutations status (exon 2,3,4) and N-RAS mutation status (Exon 2,3,4) by Real-Time PCR (Polymerase Chain Reaction) method. Results: As a result of this study, Kirsten-RAS mutation was found 48% and N-RAS mutation was 1.92%. The most common Kirsten-RAS mutations were in codon 12. The distribution of codon 12 mutations were obtained as G12V (25%), G12D (23%), G12C (14.5%). Conclusion: In our study, the frequencies of Kirsten-RAS and N-RAS mutations were compitable with similar reports. Our results have supported that testing RAS genes mutations have a vital role in identifying patients who benefit from Epidermal Growth Factor Receptor- targeted therapy.

Keywords

• Metastatic Colorectal Cancer
• RAS oncogene
• KRAS
• NRAS
• EGFR-targeted therapy

Metastatik Kolorektal Kanserli Hastalarda KRAS/NRAS Gen Mutasyon Profilleri

Abstract

Amaç: RAS genleri, Epidermal Büyüme Faktörü Reseptörü (EGFR) tarafından indüklenen RAS-MAPK Sinyal yolağının bir üyesidir. Bu yolaktaki genlerde meydana gelen mutasyonlar kanser gelişimini tetiklemektedir. Kolorektal kanserde (KRK), RAS genlerinde meydana gelen mutasyonlar EGFR hedefli tedaviye karşı direnç gelişimine neden olur. EGFR monoklonal antikorları, kemoterapötik ajanlar olarak metastatik kolorektal kanser tedavisinde yaygın şekilde kullanılmaktadır. KRAS mutasyonları KRK’nın 30-50%’sinde, NRAS mutasyonları ise 2-3%’ünde bulunur. Bu çalışmada, KRK’lı hastalarda KRAS/NRAS mutasyonlarını analiz etmeyi amaçladık. Yöntem: EGFR-hedefli tedaviye direnç gösteren 100 metastatik KRK hastası, Real-Time Polimeraz Zincir Reaksiyonu yöntemi ile KRAS mutasyonu (ekzon 2, 3, 4) ve NRAS mutasyonu (ekzon 2, 3, 4) durumu için tarandı. Bulgular: Bu çalışma sonucunda, KRAS mutasyonu oranı 48% ve NRAS mutasyonu oranı 1,92% olarak bulundu. En yaygın KRAS mutasyonları kodon 12’de saptandı. Kodon 12 mutasyonlarının dağılımı G12V (25%), G12D (23%), G12C (14,5%) olarak elde edildi. Sonuç: Çalışmamızda saptanan KRAS ve NRAS mutasyon sıklıkları benzer raporlar ile uyumlu bulundu. Sonuçlarımız, RAS mutasyonlarının test edilmesinin EGFR-hedefli tedaviden fayda sağlayacak hastaları belirlemede hayati rolünü desteklemektedir.

Keywords

• KRAS
• NRAS
• EGRF-hedefli tedavi
• Metastatik kolorektal kanser
• RAS onkogeni

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