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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Colorectal cancer,MGMT,promoter methylation,Iranian patients
- چکیده:
- چکیده انگلیسی: 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.- انتشار مقاله: 31-03-1396
- نویسندگان: Mahvash Alizadeh Naini,Soudabeh Kavousipour,Maryam Hasanzarini,Amir Nasrollah,Ahmad Monabati,Pooneh Mokarram
- مشاهده