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Asian Pacific Journal of Cancer Prevention
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Alizadeh Naini, M., Kavousipour, S., Hasanzarini, M., Nasrollah, A., Monabati, A., Mokarram, P. (2018). O6-Methyguanine-DNA Methyl Transferase (MGMT) Promoter Methylation in Serum DNA of Iranian Patients with Colorectal Cancer. Asian Pacific Journal of Cancer Prevention, 19(5), 1223-1227. doi: 10.22034/APJCP.2018.19.5.1223
Mahvash Alizadeh Naini; Soudabeh Kavousipour; Maryam Hasanzarini; Amir Nasrollah; Ahmad Monabati; Pooneh Mokarram. "O6-Methyguanine-DNA Methyl Transferase (MGMT) Promoter Methylation in Serum DNA of Iranian Patients with Colorectal Cancer". Asian Pacific Journal of Cancer Prevention, 19, 5, 2018, 1223-1227. doi: 10.22034/APJCP.2018.19.5.1223
Alizadeh Naini, M., Kavousipour, S., Hasanzarini, M., Nasrollah, A., Monabati, A., Mokarram, P. (2018). 'O6-Methyguanine-DNA Methyl Transferase (MGMT) Promoter Methylation in Serum DNA of Iranian Patients with Colorectal Cancer', Asian Pacific Journal of Cancer Prevention, 19(5), pp. 1223-1227. doi: 10.22034/APJCP.2018.19.5.1223
Alizadeh Naini, M., Kavousipour, S., Hasanzarini, M., Nasrollah, A., Monabati, A., Mokarram, P. O6-Methyguanine-DNA Methyl Transferase (MGMT) Promoter Methylation in Serum DNA of Iranian Patients with Colorectal Cancer. Asian Pacific Journal of Cancer Prevention, 2018; 19(5): 1223-1227. doi: 10.22034/APJCP.2018.19.5.1223

O6-Methyguanine-DNA Methyl Transferase (MGMT) Promoter Methylation in Serum DNA of Iranian Patients with Colorectal Cancer

Article 14, Volume 19, Issue 5, May 2018, Page 1223-1227  XML PDF (292.72 K)
Document Type: Research Articles
DOI: 10.22034/APJCP.2018.19.5.1223
Authors
Mahvash Alizadeh Naini1, 2; Soudabeh Kavousipour3; Maryam Hasanzarini2, 4; Amir Nasrollah2; Ahmad Monabati5; Pooneh Mokarram email 6, 7
1Gastroenterohepatology Research Center, Nemazi Hospital, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
2Department of Internal Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
3Department of Biotechnology, School of Advanced Medical Science and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
4Department of Internal Medicine Hamadan University of Medical Sciences, School of Medicine, Hamedan, Iran.
5Department of Pathology, School of Medicine, Shiraz University of Medical sciences, Shiraz, Iran.
6Colorectal Research Center, Nemazi hospital, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
7Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Receive Date: 21 June 2017,  Revise Date: 25 September 2017,  Accept Date: 05 April 2018 
Abstract
Introduction: Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide but current molecular targeted
therapy is not providing major success in CRC treatment, so early detection by non-invasive methods continues to
be vital. Aberrant methylation of CpG islands in promoter regions is associated with inactivation of various tumor
suppressor genes. O6-methyguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that removes mutagenic
and cytotoxic adducts from O6-guanine in DNA. Aberrant hypermethylation of the MGMT promoter has been
associated with lack of mRNA expression, with concomitant loss of protein content and enzyme activity. AIM: Our
aim was to determine whether MGMT promoter methylation might be detectable in circulating free DNA in the serum
of CRC patients and normal individuals using a methylation specific (MSP) polymerase chain reaction (PCR) method.
Methods: A total of 70 subjects were enrolled in the study. Of these, 30 patients who were diagnosed previously as
untreated colon adenocarcinoma by a gastroenterologist and the other 40 were nearly age-matched individuals who had
a normal colonoscopic evaluation (except for hemorrhoids or fissures) and normal pathologic reports. After bisulphite
modification of DNA, serum samples were examined for MGMT promoter methylation using MSP. Results: Ninety
percent of CRC patients had MGMT promoter hypermethylation as compared to no methylation in normal subjects’
serum. Most of the cancers were stage П and moderately differentiated adenocarcinomas; nearly 60% were found in
the left colon. No statistically significant correlation was found between the promoter methylation status and gender
and age. Discussion and Conclusions: MGMT hypermethylation can be detected in free circulating DNA in serum of
CRC patients and can be used “as a clinical biomarker” for early diagnosis and prognostic assessment of the disease.
Our data confirm previous studies indicating utility for free circulating DNA as a serum biomarker for early detection,
diagnosis and monitoring of CRC patients.
Keywords
MGMT; colorectal cancer; promoter methylation; Iranian patients
Main Subjects
Medical Biochemistry
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