title: Expression of BMP6 is associated with its methylation status in colorectal cancer tissue but lacks prognostic significance.
abstract: BACKGROUND
  The study aimed to evaluate the incidence of CpG island promoter methylation of BMP6, a member of the transforming growth factor beta family, in tissue samples from colorectal cancers (CRC) and look for its association with BMP6 expression and clinicopathological correlation.
  
  
  METHODS
  Methylation specific PCR for the BMP6 promoter region was performed with 85 frozen tissue samples of CRC and 45 of normal colon. Methylation status of MLH1 was also determined by the same method. Expression of BMP6 was evaluated by immunohistochemistry (IHC), using Allred's scoring system. The methylation status was analyzed against clinical and pathological parameters in CRC.
  
  
  RESULTS
  The study revealed BMP6 hypermethylation in 34 of 85 tumor specimens (40%), and 15 out of 45 normal tissue samples from CRC (33%). The incidence of hypermethylation was inversely correlated with IHC score. Allred's scores of 7 or more were correlated with lower frequency of BMP6 hypermethylation (29% compared to 50% in the remaining, p-value 0.049). However, there was no association between hypermethylation status and any clinicopathological parameters. The methylation status of BMP6 was not correlated with that of MLH1, a key methylation determinant in CRC. On survival analysis, there was no significant difference in progress-free survival (PFS) between the cases with and without hypermethylation (2-year PFS 74% and 76%, respectively).
  
  
  CONCLUSIONS
  CpG island methylation of BMP6 is found in high frequency in CRC and this epigenetic event is associated with suppressed protein expression in the tumor tissue. However, the marker is not associated with tumor progression of the disease.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand E-mail : surasak.sa@psu.ac.th.
authors.forename: Patcharaporn
authors.initials: P
authors.lastname: Sangplod
authors.forename: Samornmas
authors.initials: S
authors.lastname: Kanngurn
authors.forename: Teeranut
authors.initials: T
authors.lastname: Boonpipattanapong
authors.forename: Pritsana
authors.initials: P
authors.lastname: Ruangrat
authors.forename: Surasak
authors.initials: S
authors.lastname: Sangkhathat
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C525816:BMP6 protein, human; D055418:Bone Morphogenetic Protein 6; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1