title: Protein tyrosine phosphatase receptor-like genes are frequently hypermethylated in sporadic colorectal cancer.
abstract: The activity of phosphatases could be influenced by genetic, as well as epigenetic alterations. In our study, we have investigated the methylation status of four PTPRs: PTPRM, PTPRT, PTPRR and PTPRZ1, which were pre-selected using microarray techniques as being alternatively methylated in sporadic colorectal cancer (CRC). The analyses were carried out on 131 surgical specimens obtained from sporadic CRC patients. The methylation status of the four genes was examined using methyl specific PCR (MSP). The analysis of promoter methylation using an Illumina 27K microarray revealed four protein tyrosine phosphatases PTPRM, PTPRT, PTPRR and PTPRZ1 as being hypermethylated with β-value ≥0.2 and P≤0.05. Subsequent analysis using MSP confirmed these observations-the frequency of promoter methylation was significantly higher in tumor cells compared with matched normal tissue for each of the analyzed genes. There was no association observed between the methylation status of PTPRs and either CIMP, K-ras (codon 12) and BRAF (exon 15, V600E) mutations or tumor localization (proximal/distal). The results of our study show a statistically significant difference between promoter methylation in cancerous and healthy tissue. This result supports the hypothesis that the PTPR family has an important role in the etiology of CRC.
authors.affiliation: Department of Genetics, Wroclaw Medical University, Wroclaw, Poland. izabela.laczmanska@am.wroc.pl
authors.forename: Izabela
authors.initials: I
authors.lastname: Laczmanska
authors.forename: Pawel
authors.initials: P
authors.lastname: Karpinski
authors.forename: Marek
authors.initials: M
authors.lastname: Bebenek
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sedziak
authors.forename: David
authors.initials: D
authors.lastname: Ramsey
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Szmida
authors.forename: Maria M
authors.initials: MM
authors.lastname: Sasiadek
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D054557:Receptor-Like Protein Tyrosine Phosphatases / Q000235:genetics*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7 / Q000235:genetics
chemical_list: C516859:PTPRM protein, human; C513469:PTPRR protein, human; C516865:PTPRT protein, human; C516895:PTPRZ1 protein, human; D054557:Receptor-Like Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7