:: Volume 10, Issue 1 (Int J Mol Cell Med (In Press) 2021) ::
Int J Mol Cell Med 2021, 10(1): 0-0 Back to browse issues page
Telomerase Dysfunction in the Tumorigenesis of Genetic Disorders
Maha Mohamed Farid Aq1, Seham Abd-El Ghafour Bahget1, Naglaa Kholoussi2 , Ghada Mohamed El Hossiny Abdel-Salam3 , Haiam Abdel Raouf 4, Maha Mohamed Eid5 , Rania El-Bialy Esmail2
1- Faculty of Medicine for Girls, Al Azhar University, Cairo, Egypt.
2- Immunogenetic Department, National Research Centre, Cairo, Egypt.
3- Clinical Genetic Department, National Research Centre, Cairo, Egypt.
4- Immunogenetic Department, National Research Centre, Cairo, Egypt. , haiamabdelraouf@gmail.com
5- Cytogenetic Department, National Research Centre, Cairo, Egypt.
Abstract:   (214 Views)

Telomeres are nucleoprotein complexes present at the ends of chromosome to maintain its integrity. Telomere length is maintained by an enzyme called "telomerase". Thus, telomerase activity and telomere length are crucial for the initiation of cancer and tumors survival. Also, oxidative stress will cause DNA, protein, and/or lipid damage, which end with changes in chromosome instability, genetic mutation, and may affect cell growth and lead to cancer. Some genetic diseases such as chromosomal instability syndrome, overgrowth syndrome, and neurofibromatosis make the patients at higher risk for developing different types of cancers. Therefore, we aimed to estimate telomerase activity and oxidative stress in these patients. Blood samples were collected from 31 patients (10 with neurofibromatosis, 11 with chromosomal breakage, and 10 with overgrowth syndrome) and 12 healthy subjects. Blood hTERT mRNA was detected by real-time quantitative reverse-transcription PCR (RT-qPCR). All patients were subjected to chromosomal examination and chromosome breakage study using diepoxybutane method.  Moreover, serum glutathione (GSH), glutathione-s- transferase (GST) activity and nitric oxide (NO) levels were measured among control and patients groups. Receiver operating characteristic (ROC) curve was drawn to evaluate the efficiency of telomerase activity as biomarker for the prediction of cancer occurrence. The relative telomerase activity in neurofibromatosis patients was significantly higher than controls (P = 0.014), while it was non-significantly higher in chromosomal breakage and overgrowth patients (P = 0.424 and 0.129, respectively). NO levels in neurofibromatosis, chromosomal breakage and overgrowth patients were significantly increased with respect to control (P = 0.021, 0.002, 0.050, respectively). GSH levels were non-significantly lower in neurofibromatosis and chromosomal breakage patients in comparison with the control group, while it remained unchanged in overgrowth patients. The GST activity was significantly up-regulated in all patients groups in comparison with the control group (P = 0.001, 0.009, and 0.025, respectively). Chromosomal examination revealed normal karyotype in all four chromosomal breakage patients with positive diepoxybutane test. The results of the present study revealed altered telomerase activity and oxidative stress in the studied genetic disorders. More research with a larger number of patients is required to confirm whether this alteration is related to cancer occurrence risk.

Keywords: Telomerase, genetic disorder, neurofibromatosis, chromosomal breakage, overgrowth, oxidative stress
Type of Study: Original Article | Subject: Genetics & Disease
Received: 2020/10/14 | Accepted: 2021/02/25 | Published: 2021/01/21

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Volume 10, Issue 1 (Int J Mol Cell Med (In Press) 2021) Back to browse issues page