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Sporadik Medüller Tiroid Kanserli Bir Hastada Nadir Görülen RET Proto-Onkogen Mutasyonu: D631Y

Amaç: Multipl endokrin neoplazi tip 2 (MEN2), otozomal dominant kalıtım sergileyen bir sendromolup, germ hattında meydana gelen yanlış anlamlı RET proto-onkogen mutasyonları ile ilişkilendirilmiştir.Mutasyon taşıyıcılarının yaklaşık %90’ının medüller tiroid karsinomu (MTK) geliştirdiği bilinmektedir.Hastalarda RET mutasyon taraması ile genetik tanı sağlanmakta ve ailede henüz semptomgöstermeyen bireylerin mutasyon tipine göre önleyici cerrahi müdahaleye yönlendirilmeleri sağlanabilmektedir.Bu bağlamda, çalışmamız sporadik MTK teşhisli bireyin klinik takiplerinin sağlanması veiki oğlu ile birlikte RET proto-onkogen genetik tanılarının gerçekleştirilmesini amaçlamıştır.Yöntem: İndeks vakanın detaylı klinik değerlendirmeleri ile pre-operatuvar ve post-operatif histopatolojikincelemeleri gerçekleştirilmiştir. Boyun ultrasonografisi ve biyokimyasal değerlendirmeler dedahil olmak üzere rutin klinik takip yapılmıştır.RET proto-onkogenin rutin genetik tanısı, genin 10, 11, 13-16’ıncı ekzonlarının PZR amplifikasyonunutakiben Sanger dizilemesi yöntemleri ile gerçekleştirilmiştir. Mutasyon taşıyan ekzon hastanınasemptomatik iki oğlunda taranmıştır.Bulgular: İndeks vaka klinik incelemeler ve histopatolojik tanı ile sporadik MTK tanısı almıştır. RETgen mutasyon taraması sonucunda hastanın 11. ekzonunda c.1891G>T (D631Y) mutasyonu ile 11 ve13. ekzonlarında sırasıyla rs1799939 ve rs1800861 polimorfizmleri tespit edilmiştir. Hastanın her ikioğlu da RET geni 11. ekzon için taranmış ancak mutasyon taşımadıkları bildirilmiştir.Sonuç: Genetik tanı hem indeks vakanın sporadik MTK tanısını kesinleştirmiş hem de oğullarındasağlıklı olduğunu göstermiştir. Bu çalışma, literatürde ilk defa feokromasitomaya eşlik etmeyen sporadikmedüller tiroid kanserli bir olguda D631Y mutasyon varlığını göstermektedir.

Anahtar Kelimeler:

MEN2, Medüller tiroid karsinomu, RET proto-onkogeni, D631Y, mutasyon

A RARE RET PROTO-ONCOGENE MUTATION IN A SPORADIC MEDULLARY THYROID CARCINOMA: D631Y

Objectives: Multiple endocrine neoplasia type 2 (MEN2) syndrome is associated with germ-linemissense mutations in RET proto-oncogene, inherited in an autosomal dominant manner. Approximately90% of RET mutations were shown to develop medullary thyroid carcinoma (MTK). Genetictesting is accomplished through RET mutation screen and asymptomatic first degree relatives of indexcases are recommended to be tested for preventative surgical operations. Thus, we aimed to performclinical follow-up of a sporadic MTK case, as well as to carry out RET proto-oncogen genetic diagnosison the index case and her two sons.Materials and Methods: Index case has been subjected to detailed clinical evaluations, as well asto pre- and post-operative hystopathological examinations. Routine clinical follow-up including neckultrasonography and biochemical evaluations have been performed. RET proto-oncogene routinediag-nostic test was performed on 10, 11, 13-16th exons of the gene through PCR-amplificationfollowed by Sanger sequencing. Exon with a mutation was screened on index cases’ two sons.Results: Clinical evaluations diagnosed index case as MTK. RET genetic screen revealed c.1891G>T(D631Y) in 11th exon confirming diagnosis. The two sons were found negative for RET gene mutationsin their 11th exons.Conclusion: Genetic diagnosis both confirmed clinical diagnosis of the index case and showed thatthe sons are healthy. This is the first report of a D631Y mutation in a case of sporadic medullary thyroidcancer without pheochromocytoma in the literature.

Keywords:

MEN2, Medullary thyroid carcinoma, RET proto-oncogene, D631Y, mutation,

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