title: Sensitive and Noninvasive Detection of Aberrant SFRP2 and MGMT-B Methylation in Iranian Patients with Colon Polyps.
abstract: BACKGROUND
  The pathogenesis of sporadic colorectal cancer (CRC) is influenced by the patient genetic background and environmental factors. Based on prior understanding, these are classified in two major pathways of genetic instability. Microsatellite instability (MSI) and CPG island methylator phenotype (CIMP) are categorized as features of the hypermethylated prototype, and chromosomal instability (CIN) is known to be indicative of the non-hypermethylated category. Secreted frizzled related protein 2 (SFRP2), APC1A in WNT signaling pathway and the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), are frequently hypermethylated in colorectal cancer. Detection of methylated DNA as a biomarker by easy and inexpensive methods might improve the quality of life of patients with CRC via early detection of cancer or a precancerous condition.
  
  
  OBJECTIVE
  To evaluate the rate of SFRP2 and MGMT hypermethylation in both polyp tissue and serum of patients in south Iran as compared with matched control normal population corresponding samples.
  
  
  METHODS
  Methylation-specific PCR was used to detect hypermethylation in DNA extracted from 48 polypoid tissue samples and 25 healthy individuals.
  
  
  RESULTS
  Of total polyp samples, 89.5% had at least one promoter gene hypermethylation. The most frequent methylated locus was SFRP2 followed by MGMT-B (81.2 and 66.6 percent respectively). Serologic detection of hypermethylation was 95% sensitive as compared with polyp tissue. No hypermethylation was detected in normal tissue and serum and its detection in patients with polyps, especially of serrated type, was specific.
  
  
  CONCLUSIONS
  Serologic investigation for detection of MGMT-B, SFRP2 hypermethylation could facilitate prioritization of high risk patients for colonoscopic polyp detection and excision.
authors.affiliation: Department of Internal Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran E-mail : Mokaram2@gmail.com.
authors.forename: M Alizade
authors.initials: MA
authors.lastname: Naini
authors.forename: P
authors.initials: P
authors.lastname: Mokarram
authors.forename: S
authors.initials: S
authors.lastname: Kavousipour
authors.forename: N
authors.initials: N
authors.lastname: Zare
authors.forename: A
authors.initials: A
authors.lastname: Atapour
authors.forename: M Hassan
authors.initials: MH
authors.lastname: Zarin1
authors.forename: G
authors.initials: G
authors.lastname: Mehrabani
authors.forename: M
authors.initials: M
authors.lastname: Borji
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003111:Colonic Polyps / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011230:Precancerous Conditions / Q000097:blood / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D014408:Biomarkers, Tumor; D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C515491:MGMT protein, human