Nadhum J. ISMAİEL, Hazha J. HİDAYAT, Rozhgar A. KHAİLANY

Molecular genetics of renal cell carcinoma: polybromo 1 and set domain containing 2 genes

Amaç: Renal hücreli karsinoma (RCC) 3. kromozomun kısa kolundaki tekrar kayıpları ile karakterizedir. Klasik olarak Von Hippel Lindau sendromunda sadece RCC gen mutasyonu sıklıkla görülmekteydi. Son zamanlarda PBRM1 ve SETD2 yi içeren histon modifikasyon ve kromatin remodeling genlerinde de mutasyonlar yoğunlukla tanımlanmıştır. Bu çalışmada moleküler teknikler ile PBRM1 ve SETD2 genleri ile RCC arasındaki muhtemel ilişkiyi belirlenmesi amaçlanmıştır. Gereç ve Yöntem: RCC hastalarından alınan normal ve tümöral dokuda PBRM1 ve SETD2 genlerinin mRNA ekspresyon seviyeleri ve olası mutasyonları nükleotid sekanslama ve Reverse transkripsiyon polimeraz zincir reaksiyonu (RT- PCR) ile belirlendi. Bulgular: Kontrol ile kıyaslandığında her iki gen için de mRNA ekspresyon değerleri tümöral dokuda anlamlı derecede azalmıştır. Mutasyon analiz sonuçlarına göre 1 hastanın SETD2 geninin 12 nolu exonunda tek insersiyon nükleotid polimorfizmi saptandı. Sonuç: PBRM1 ve SETD2 mRNA ekspresyon seviyelerinin azalması RCC gelişmesi için risk faktörü olabilir. Gelecekte RCC de SETD2 ve PBRM1 in dışında farklı genlerinde araştırılması gerekmektedir.

Renal hücreli karsinomun moleküler genetiği: polybromo 1 ve SET domain içeren 2 gen

Purpose: Renal cell carcinoma (RCC) is genetically characterized by the recurrent loss of the short arm of chromosome 3. Classically, Von Hippel Lindau (VHL) was the only frequently mutated gene in RCC. Recently, several novel frequent mutations of histone modifying and chromatin remodeling genes, including PBRM1 and SETD2, were identified. In the present study, we aimed to determine the possible relationship between PBRM1 and SETD2 genes, and renal cell carcinoma by molecular techniques. Material and Methods: Screening possible mutation and determining mRNA expression level of PBRM1 and SETD2 genes in 20 pairs of tumor and normal samples of RCC patients were performed by nucleotide sequencer and reverse transcription- polymerase chain reaction (RTPCR). Results: The mRNA expression levels of both genes were significantly reduced in tumor samples when compared with the control samples. As a result of mutational analysis, a single insertion nucleotide polymorphism in exon 12 of SETD2 gene was detected in one patient. Conclusion: Reduced mRNA expression level of PBRM1 and SETD2 might be risk factor for RCC development. Further analysis is warranted to investigate responsible genes rather than PBRM1 and SETD2 in RCC.

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