Turkiye Klinikleri Journal of Endocrinology

.: ORIGINAL RESEARCH
Screening of Three Exons of the RET Proto-oncogene in Turkish Patients with Papillary Thyroid Carcinoma
Papiller Tiroid Kanserli Türk Olgularda RET Proto-onkogenine Ait Üç Ekzonun Görüntülenmesi
Naciye Selcen BAYRAMCIa, Lütfiye Yasemin KOÇ BİLİRb, Leyla AÇIKa, Gülin UÇMAK VURALc, Mehmet KILIÇd, Mesut TEZd, Mahmut KOÇd, Nur ERÇAKMAKc
aDepartment of Biology, Gazi University, Faculty of Arts and Science, bDepartment of Biology, Ankara University, Faculty of Science, cClinic of Nuclear Medicine, Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, dClinic of 5th General Surgery, Ankara Numune Education and Research Hospital, Ankara
Turkiye Klinikleri J Endocrin. 2010;5(2):54-61
Article Language: EN
Full Text
ABSTRACT
Objective: The RET proto-oncogene involvement in thyroid carcinomas has been reported in different populations. In this study, peripheral blood DNA of papillary thyroid carcinoma (PTC) patients and healthy people for germline in RET exons 10, 11 and 13 were studied. Material and Methods: Peripheral blood samples were obtained from 82 PTC patients and 85 healthy controls and genomic DNA was isolated, after that Polymerase Chain Reaction (PCR) and sequencing were used for mutations analysis. Results: Molecular analyses revealed probable mutations in exon 11 of the RET gene at a codons 630, 632, 633, 634, 635, 637, 659, 662, 697, 701, 702, and 703. In all of 13.41% of the patients had mutation in exon 11 and 3.65 % of the patients had mutation in exon 13. Mutations in exon 13 were at codons 765, 770, and 795. Single nucleotide polymorphisms (SNPs) were detected at codon 769 (26.82%) and 763 (1.2%) in exon 13, and 691 (3.65%) and 631 (1.2%) in exon 11. Conclusion: It was observed that four of 82 PTC patients had Cys630Ser (TGC→AGC, 5.9%), which was the most common mutation at codon 630 in exon 11. Moreover, Cys630Ser mutation is associated with medullary thyroid carcinomas; however, genetic testing in the present study diagnosed this mutation in four patients with PTC. The finding of large number of SNPs at codon 769 in exon 13 in PTC is important.

Keywords: Adenocarcinoma, papillary; polymerase chain reaction
ÖZET
Amaç: Farklı populasyonlarda tiroid kanserleri ile RET proto-onkogen ilişkisi bildirilmiştir. Çalışmamızda papiller tiroid kanserli (PTC) hastalarda ve sağlıklı kontrol grubunda RET proto-onkogenine ait 10., 11. ve 13. ekzon bölgelerinde germ-line mutasyonlar araştırılmıştır. Gereç ve Yöntemler: Papiller tiroid kanserli 82 hasta ve 85 sağlıklı kontrolden periferal kan örnekleri alınıp ve genomik DNA izole edilmiş ve daha sonra mutasyon durumları Polimeraz Zincir Reaksiyonu (PCR) ve DNA dizi analizi ile gösterilmiştir. Bulgular: Moleküler analizler RET geninin 11. ekzon bölgesindeki olası mutasyonların kodon 630, 632, 633, 634, 635, 637, 659, 662, 697, 701, 702 ve 703'te olduğunu göstermiştir. Hastaların %13.41'inde 11. ekzon bölgesinde %3.65'de 13. ekzon bölgesinde mutasyon tespit edilmiştir. Ekzon 13 bölgesindeki mutasyonlar ise kodon 765, 770 ve 795'te saptanmıştır. Hastaların ekzon 13 bölgesinde yer alan kodon 769 (%26.82) ve 763 (%1.2)'te ve ekzon 11 bölgesinde kodon 691 (%3.65) ve 631 (%1.2)'de tek nükleotid polimorfizmi (SNP) tespit edilmiştir. Sonuç: Sekseniki olgu içeren PTC hasta grubundan, dört hastada tespit etmiş olduğumuz Cys630Ser (TGC→AGC, %5.9) mutasyonu 11. ekzonun 630. kodon bölgesinde görülen en yaygın mutasyondur. Medüller tiroid kanseri ile ilişkilendirilen Cys630Ser mutasyonu, PTC tanısı konulmuş dört hastada görülmüştür. Papiller tiroid kanseri olgularına ait ekzon 13 bölgesi 769. kodonda SNP sayısının fazla olması araştırmamızın dikkate değer önemli bir sonucunu oluşturmaktadır.

Anahtar Kelimeler: Adenokarsinom, papiller; polimeraz zincir reaksiyonu

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