The evaluation of telomere length and telomerase activity measurement in Neurofibromatosis type 1 NF1 tumors

Abstract

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 speciesdependent 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. © (2023), (Refik Saydam National Public Health Agency (RSNPHA)). All Rights Reserved.