Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
Analysis of BRAFV600E, KRAS Codon 12/13 and Novel Mutations in Patients with Thyroid Cancer in Blacksea Region of Turkey
Karadeniz Bölgesinde Tiroid Kanserli Hastalarda BRAFV600E, KRAS Kodon 12/13 ve Yeni Mutasyonların Analizi
Ayfer KAMALI POLATa, Zülfinaz Betül ÇELİKb, Yurdanur SÜLLÜc, Şengül TURALb, Nurten KARAb
aDepartment of General Surgery, Ondokuz Mayıs University Faculty of Medicine, Samsun, TURKEY
bDepartment of Medical Biology, Ondokuz Mayıs University Faculty of Medicine, Samsun, TURKEY
cDepartment of Pathology, Ondokuz Mayıs University Faculty of Medicine, Samsun, TURKEY
Turkiye Klinikleri J Med Sci. 2021;41(1):80-5
doi: 10.5336/medsci.2020-76105
Article Language: EN
Full Text
ABSTRACT
 Objective: The incidence of thyroid cancer in many regions of the world has been steadily increasing over the past decades. Point mutations in the B-Raf (BRAF) and RAS proto-oncogenes are crucial in the molecular pathogenesis of thyroid cancers. In this study, it was aimed to investigate the BRAFV600E and KRAS codon 12/13 mutations in thyroid cancer patients of the Turkish population. Material and Methods: In this study, totally 32 cases with thyroid cancer were investigated. Ten of the paraffin-embedded thyroid cancer tissues and 22 of peripheral blood samples from patients were included in the study. Genomic DNA was extracted from the paraffin-embedded sections and peripheral blood samples, and then polymerase chain reaction and DNA sequencing were performed for mutation analysis of BRAF and KRAS genes. Results: BRAFV600E mutations were found in 13 (40.6%) patients, and 19 patients (59.4%) had wild-type profiles. G12N, G12V, and G13V mutations that are frequently seen in KRAS were not observed, but four new mutations (K16E, L19G, E31D, and M1I) were found in the current cohort. Conclusion: BRAFV600E mutation was detected in patients with thyroid cancer, and four new mutations, which are in the GTP binding regions of the protein, were detected in the KRAS gene. These new mutations might be related to papillary thyroid cancer.

Keywords: Proto-oncogene proteins B-Raf; genes, Ras; thyroid cancer, papillary; mutation
ÖZET
 Amaç: Dünyanın pek çok bölgesinde tiroid kanseri görülme sıklığı, son yıllarda sürekli olarak artmaktadır. B-Raf (BRAF) ve RAS proto-onkogenlerindeki nokta mutasyonları, tiroid kanserlerinin moleküler patogenezinde çok önemlidir. Bu çalışmada, Türk toplumundaki tiroid kanseri hastalarında BRAFV600E ve KRAS kodon 12/13 mutasyonlarının araştırılması amaçlandı. Gereç ve Yöntemler: Çalışmada, toplam 32 tiroid kanseri vakası incelendi. Parafine gömülü tiroid kanser dokularından 10'u ve hastalardan alınan periferik kan örneklerinden 22'si çalışmaya dâhil edildi. Parafine gömülü kesitlerden ve periferik kan örneklerinden genomik DNA ekstrakte edildikten sonra BRAF ve KRAS genlerinin mutasyon analizi için polimeraz zincir reaksiyonu ve DNA dizi analizi yapıldı. Bulgular: BRAFV600E mutasyonları 13 (%40,6) hastada bulundu ve 19 (%59,4) hasta ise yabanıl tip profile sahipti. KRAS'ta sıklıkla görülen G12N, G12V ve G13V mutasyonları bu kohortta gözlenmedi, ancak 4 yeni mutasyon (K16E, L19G, E31D ve M1I) bulundu. Sonuç: Tiroid kanserli hastalarda BRAFV600E mutasyonu ve KRAS geninde proteinin GTP bağlanma bölgelerinde meydana gelen 4 yeni mutasyon tespit edildi. Bu yeni mutasyonlar papiller tiroid kanseriyle ilişkili olabilir.

Anahtar Kelimeler: Proto-onkogen proteinleri B-Raf; genler, Ras; tiroid kanser, papiller; mutasyon
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