title: Stool methylated DNA markers decrease following colorectal cancer resection--implications for surveillance.
abstract: BACKGROUND
  Molecular changes associated with colorectal cancer (CRC) are detected by stool deoxyribonucleic acid testing but could persist following tumor resection.
  
  
  OBJECTIVE
  We sought to determine whether methylated gene markers in stool normalize after CRC resection.
  
  
  METHODS
  We studied stools from 22 CRC cases before and after subtotal resection and from 80 colonoscopy-normal controls. In blinded fashion, target genes (methylated NDRG4 and BMP3) were captured from stool supernatant, bisulfite-treated, and assayed by quantitative allele-specific real-time target and signal amplification. Results were dichotomized at 95% specificity cutoffs.
  
  
  RESULTS
  Among CRC cases, median methylated NDRG4 and BMP3 levels decreased dramatically (4- to 15-fold) following resection, p = 0.003 and p < 0.0001, respectively. Among the 14 cases with elevated preoperative levels, 13 (93%) fell into the normal range after surgery, p = 0.0002. A case whose stool methylated NDRG4 level increased sharply after surgery was found to have recurrent CRC.
  
  
  CONCLUSIONS
  Methylated gene marker levels clear from stool following CRC resection unless disease is present. Postoperative stool marker levels are informative and may be of value in surveillance.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN, 55905, USA, kisiel.john@mayo.edu.
authors.forename: John B
authors.initials: JB
authors.lastname: Kisiel
authors.forename: Tracy C
authors.initials: TC
authors.lastname: Yab
authors.forename: William R
authors.initials: WR
authors.lastname: Taylor
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Mahoney
authors.forename: David A
authors.initials: DA
authors.lastname: Ahlquist
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D055398:Bone Morphogenetic Protein 3 / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000601:surgery; D019175:DNA Methylation; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011159:Population Surveillance
chemical_list: C525757:BMP3 protein, human; D014408:Biomarkers, Tumor; D055398:Bone Morphogenetic Protein 3; D009124:Muscle Proteins; C431705:NDRG4 protein, human; D009419:Nerve Tissue Proteins