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
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.
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