title: Methylation of the polycomb group target genes is a possible biomarker for favorable prognosis in colorectal cancer.
abstract: BACKGROUND
  Colorectal cancer (CRC) is the second most common cancer in the Kingdom of Saudi Arabia with ever increasing incidence rates. DNA methylation is a common event in CRC where it is now considered an important phenomenon in CRC carcinogenesis and useful for the classification and prognosis of CRC.
  
  
  METHODS
  To gain insight into the molecular mechanisms underpinning CRC in Saudi Arabian patients, we profiled the DNA methylation frequency of key genes (MLH1, MSH2, RASSF1A, SLIT2, HIC1, MGMT, SFRP1, MYOD1, APC, CDKN2A, as well as five CIMP markers) in 120 sporadic CRC cases. CRC tumors originating from the rectum, left, and right colons are represented in this cohort of formalin-fixed paraffin-embedded tissues.
  
  
  RESULTS
  The most common methylation frequency was detected in the polycomb group target genes (PCGT) including SFRP1 (70%), MYOD1 (60.8%), HIC1 (61.7%), and SLIT2 (56.7%). In addition, MGMT methylation was detected at a high frequency (68.3%). RASSF1A, APC, and CDKN2A methylation frequencies were 42.5%, 25%, and 32.8%, respectively. K-means clustering analysis of the methylation events results in the clustering of the CRC samples into three groups depending on the level of methylation detected.
  
  
  CONCLUSIONS
  Group II (PCGT methylation and CIMP-negative) methylation signature carried a favorable prognosis for male patients, whereas older patients with group I rare methylation signature have a potentially poorer clinical outcome.
  
  
  CONCLUSIONS
  Methylation of the PCGT genes along with RASSF1A, APC, and MGMT can be potentially used as a new biomarker for the classification and prognosis of CRC tumors and independently of where the tumor has originated.
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Fahad Medical Research Center, King Abdulaziz University, P.O. Box 80216, 21589 Jeddah, Kingdom of Saudi Arabia. adallol@kau.edu.sa
authors.forename: Ashraf
authors.initials: A
authors.lastname: Dallol
authors.forename: Jaudah
authors.initials: J
authors.lastname: Al-Maghrabi
authors.forename: Abdelbaset
authors.initials: A
authors.lastname: Buhmeida
authors.forename: Mamdooh A
authors.initials: MA
authors.lastname: Gari
authors.forename: Adeel G
authors.initials: AG
authors.lastname: Chaudhary
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Schulten
authors.forename: Adel M
authors.initials: AM
authors.lastname: Abuzenadah
authors.forename: Mahmoud S
authors.initials: MS
authors.lastname: Al-Ahwal
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Sibiany
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Al-Qahtani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D063146:Polycomb-Group Proteins / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D012529:Saudi Arabia; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes