International Journal of Molecular and Cellular Medicine
مجله بین المللی سلولی و مولکولی
Int J Mol Cell Med
Medical Sciences
http://ijmcmed.org
1
admin
2251-9637
2251-9645
10.22088/IJMCM.BUMS
en
jalali
1399
10
1
gregorian
2021
1
1
10
1
online
1
fulltext
en
Telomerase Dysfunction in the Tumorigenesis of Genetic Disorders
Genetics & Disease
Genetics & Disease
Original Article
Original Article
<p style="font-style:normal;">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 the control and patients groups. Receiver operating characteristic (ROC) curve was drawn to evaluate the efficiency of telomerase activity as a biomarker for the prediction of cancer occurrence. The relative telomerase activity in neurofibromatosis patients was significantly highe<a name="_Hlk484272034">r than controls (P = 0.014), while it was non-significantly higher in </a><a name="_Hlk480129232">chromosomal breakage and overgrowth patients</a> (P = 0.424 and 0.129, respectively). NO levels in neurofibromatosis, chromosomal breakage and overgrowth patients 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 upregulated in neurofibromatosis, chromosomal breakage and overgrowth 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 studies with a larger number of patients are required to confirm whether this alteration is related to cancer occurrence risk or not.</p>
Telomerase, genetic disorder, neurofibromatosis, chromosomal breakage, overgrowth, oxidative stress
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67
http://ijmcmed.org/browse.php?a_code=A-10-2550-2&slc_lang=en&sid=1
Maha Mohamed
Farid Aql
mahafarid@gmail.com
100319475328460020486
100319475328460020486
No
Faculty of Medicine for Girls, Al Azhar University, Cairo, Egypt.
Seham
Abd-El Ghafour Bahget
sehambahgat@hotmail.com
100319475328460020487
100319475328460020487
No
Faculty of Medicine for Girls, Al Azhar University, Cairo, Egypt.
Naglaa
Kholoussi
nkholoussi@gmail.com
100319475328460020488
100319475328460020488
No
Immunogenetic Department, National Research Centre, Cairo, Egypt.
Ghada Mohamed El Hossiny
Abdel-Salam
ghada.abdelsalam@gmail.com
100319475328460020489
100319475328460020489
No
Clinical Genetic Department, National Research Centre, Cairo, Egypt.
Haiam
Abdel Raouf
haiamabdelraouf@gmail.com
100319475328460020490
100319475328460020490
Yes
Immunogenetic Department, National Research Centre, Cairo, Egypt.
Maha Mohamed
Eid
mahaeid67@gmail.com
100319475328460020491
100319475328460020491
No
Cytogenetic Department, National Research Centre, Cairo, Egypt.
Rania
El-Bialy Esmail
raniashaisha@gmail.com
100319475328460020492
100319475328460020492
No
Immunogenetic Department, National Research Centre, Cairo, Egypt.