The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors
Yıl: 2023 Cilt: 80 Sayı: 3 Sayfa Aralığı: 365 - 372 Metin Dili: İngilizce DOI: 10.5505/TurkHijyen.2023.59002 İndeks Tarihi: 28-09-2023
The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors
Öz: Objective: Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that affects 1 in 2,500 people worldwide. The disease is developed due to the occurrence of mutations in NF1 gene. NF1 gene is coding cytoplasmic protein which is negative regulator of RAS proteins. The loss of neurofibromin results in activation of RAS cascade and cell proliferation. For this reason, NF1 gene is categorized as tumor suppressor gene. It is clinically characterized by cafe-au-lait spots, Lisch nodules, axillary and inguinal freckling, multiple peripheral nerve tumors, bone lesions, and a predisposition to malignancy. Variations in NF1 mutations may not correlate with the variations in clinical phenotype. This unclear genotype–phenotype correlations is assumed to be due to modifier genes. One of these modifier candidates is telomere length and telomerase activity. Telomeres are repetitive nucleotide sequences located at the ends of chromosomes and protect them from fraying and sticking to each other. The length of telomeres is shortening in each cell division. Nevertheless, this shortening can be prohibited by the enzyme telomerase which adds a species-dependent telomere repeat sequence to the 3’ end of telomeres. However, telomerase activity usually diminished after birth in somatic cells. Researches done in last years have shown the importance of telomere and telomerase activity and they are causally connected to human disease. However, the number of research on this concept for NF1 patients is very few. Methods: The DNA and proteins isolated from tumors of nine NF1 patients was analyzed by quantitative PCR based technics. Telomere length measurement were done using the DNA samples. The pathological status of tumor tissues was confirmed by routine pathological examination. Telomerase activity were evaluated from proteins isolated from acquired tumor samples. Results: Considering the preliminary results, higher telomerase activity is measured in some NF1 tumors and also variations in telomere size were detected. Conclusion: These primary data indicate that telomere length may play an important role in NF1-associated tumor’s progression and could provide information about the telomere-targeted therapeutic approaches for treatment of telomere dysfunction in the clinic.
Anahtar Kelime: Nörofibromatozis tip 1 (NF1) tümörlerinde telomer uzunluğu ve telomeraz aktivitesinin ölçülmesi ve değerlendirilmesi
Öz: Amaç: Nörofibromatozis tip 1 (NF1), dünyada her 2.500 kişiden birini etkileyen otozomal dominant bir hastalıktır. Hastalık, NF1 genindeki mutasyonlar nedeniyle gelişir. NF1 geni, RAS proteinlerinin negatif regülatörü olan sitoplazmik bir proteini kodlamaktadır. Nörofibromin kaybı, RAS kaskadının aktivasyonuna ve hücre çoğalmasına neden olur. Bu nedenle NF1 geni, tümör baskılayıcı gen olarak kategorize edilir. Klinik olarak cafe-au-lait lekeleri, Lisch nodülleri, koltuk altı ve kasık çilleri, çoklu periferik sinir tümörleri, kemik lezyonları ve maliniteye yatkınlık ile karakterizedir. NF1 mutasyonlarındaki varyasyonlar, klinik fenotipteki varyasyonlarla ilişkili olmayabilir. Bu genotip-fenotip korelasyon yokluğunun modifiye edici genlerden kaynaklandığı varsayılmaktadır. Modifiye edici gen adaylarından biri de telomer uzunluğu ve telomeraz enzim aktivitesidir. Telomerler, kromozomların uçlarında yer alan ve onları yıpranmaya ve birbirine yapışmaya karşı koruyan tekrarlayan nükleotid dizileridir. Her hücre bölünmesinde telomerlerin uzunluğu kısalır ve bu kısalma, telomerlerin 3’ ucuna telomer tekrar dizisi ekleyen telomeraz enzimi tarafından engellenebilir. Bununla birlikte, somatik hücrelerde telomeraz aktivitesi genellikle doğumdan sonra azalır. Son yıllarda yapılan araştırmalar, telomer ve telomeraz aktivitesinin önemini ve hastalıklarla ilişkili olduğunu göstermiştir. Ancak NF1 hastaları için bu kavramla ilgili araştırmalar son yıllarda başlamış olup sayısı çok azdır. Yöntem: Dokuz NF1 hastasının tümör dokularından elde edilen DNA ve protein örnekleri kantitatif PCR tabanlı tekniklerle analiz edildi. Tümör dokularının patolojik durumu, rutin patolojik inceleme ile doğrulandı. DNA örnekleri kullanılarak telomer uzunlukları ölçüldü. Telomeraz aktivitesi, elde edilen tümör örneklerinden izole edilen proteinlerden değerlendirildi. Bulgular: İlk sonuçlara bakıldığında, bazı NF1 tümörlerinde daha yüksek telomeraz aktivitesi ölçülmüş ve ayrıca telomer boyunda da varyasyonlar tespit edilmiştir. Sonuç: Bu öncül veriler, telomer uzunluğunun NF1 ile ilişkili tümörlerin ilerleme sürecinde önemli rol oynayabileceğini göstermiştir. Bu durum klinikte telomer işlev bozukluğunun tedavisi için telomer hedefli terapötik yaklaşımlar için de önemlidir.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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| APA | SHARAFI P, KILIÇ Z, ANLAR B, VARAN A, ERSOY EVANS S, VARGEL İ, YILDIRIM Ö, AYTER Ş (2023). The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors. , 365 - 372. 10.5505/TurkHijyen.2023.59002 |
| Chicago | SHARAFI Parisa,KILIÇ Zeynep,ANLAR Banu,VARAN Ali,ERSOY EVANS Sibel,VARGEL İbrahim,YILDIRIM Özlem,AYTER Şükriye The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors. (2023): 365 - 372. 10.5505/TurkHijyen.2023.59002 |
| MLA | SHARAFI Parisa,KILIÇ Zeynep,ANLAR Banu,VARAN Ali,ERSOY EVANS Sibel,VARGEL İbrahim,YILDIRIM Özlem,AYTER Şükriye The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors. , 2023, ss.365 - 372. 10.5505/TurkHijyen.2023.59002 |
| AMA | SHARAFI P,KILIÇ Z,ANLAR B,VARAN A,ERSOY EVANS S,VARGEL İ,YILDIRIM Ö,AYTER Ş The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors. . 2023; 365 - 372. 10.5505/TurkHijyen.2023.59002 |
| Vancouver | SHARAFI P,KILIÇ Z,ANLAR B,VARAN A,ERSOY EVANS S,VARGEL İ,YILDIRIM Ö,AYTER Ş The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors. . 2023; 365 - 372. 10.5505/TurkHijyen.2023.59002 |
| IEEE | SHARAFI P,KILIÇ Z,ANLAR B,VARAN A,ERSOY EVANS S,VARGEL İ,YILDIRIM Ö,AYTER Ş "The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors." , ss.365 - 372, 2023. 10.5505/TurkHijyen.2023.59002 |
| ISNAD | SHARAFI, Parisa vd. "The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors". (2023), 365-372. https://doi.org/10.5505/TurkHijyen.2023.59002 |
| APA | SHARAFI P, KILIÇ Z, ANLAR B, VARAN A, ERSOY EVANS S, VARGEL İ, YILDIRIM Ö, AYTER Ş (2023). The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors. Türk Hijyen ve Deneysel Biyoloji Dergisi, 80(3), 365 - 372. 10.5505/TurkHijyen.2023.59002 |
| Chicago | SHARAFI Parisa,KILIÇ Zeynep,ANLAR Banu,VARAN Ali,ERSOY EVANS Sibel,VARGEL İbrahim,YILDIRIM Özlem,AYTER Şükriye The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors. Türk Hijyen ve Deneysel Biyoloji Dergisi 80, no.3 (2023): 365 - 372. 10.5505/TurkHijyen.2023.59002 |
| MLA | SHARAFI Parisa,KILIÇ Zeynep,ANLAR Banu,VARAN Ali,ERSOY EVANS Sibel,VARGEL İbrahim,YILDIRIM Özlem,AYTER Şükriye The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors. Türk Hijyen ve Deneysel Biyoloji Dergisi, vol.80, no.3, 2023, ss.365 - 372. 10.5505/TurkHijyen.2023.59002 |
| AMA | SHARAFI P,KILIÇ Z,ANLAR B,VARAN A,ERSOY EVANS S,VARGEL İ,YILDIRIM Ö,AYTER Ş The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors. Türk Hijyen ve Deneysel Biyoloji Dergisi. 2023; 80(3): 365 - 372. 10.5505/TurkHijyen.2023.59002 |
| Vancouver | SHARAFI P,KILIÇ Z,ANLAR B,VARAN A,ERSOY EVANS S,VARGEL İ,YILDIRIM Ö,AYTER Ş The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors. Türk Hijyen ve Deneysel Biyoloji Dergisi. 2023; 80(3): 365 - 372. 10.5505/TurkHijyen.2023.59002 |
| IEEE | SHARAFI P,KILIÇ Z,ANLAR B,VARAN A,ERSOY EVANS S,VARGEL İ,YILDIRIM Ö,AYTER Ş "The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors." Türk Hijyen ve Deneysel Biyoloji Dergisi, 80, ss.365 - 372, 2023. 10.5505/TurkHijyen.2023.59002 |
| ISNAD | SHARAFI, Parisa vd. "The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors". Türk Hijyen ve Deneysel Biyoloji Dergisi 80/3 (2023), 365-372. https://doi.org/10.5505/TurkHijyen.2023.59002 |
