title: Genome-wide identification of OTP gene as a novel methylation marker             of breast cancer.
abstract: Aberrant DNA methylation occurs early and frequently in tumorigenesis. Identification             of DNA methylation biomarkers is a field that provides potential for improving             the clinical process of breast cancer diagnosis. We utilized a genome-wide technique,             methylated DNA isolation assay (MeDIA), in combination with high-resolution CpG             microarray analysis to identify hypermethylated genes in breast cancer. Among             differentially methylated genes between tumor and adjacent normal tissues, 3 candidate             genes (LHX2, WT1 and OTP) were finally selected through a step-wise filtering             process and examined for methylation status in normal tissues, primary tumor,             and paired adjacent normal-appearing tissues from 39 breast cancer patients. Based             on the calculated cut-off values, all genes showed significantly higher frequencies             of aberrant hypermethylation in primary tumors (43.6% for LHX2, 89.7% for WT1             and 100% for OTP, p<0.05) while frequencies were intermediate in paired adjacent             normal tissues and absent in normal tissues. On further analysis, the methylation             level in primary tumors was not significantly correlated with clinicopathological             features. Interestingly, DNA methylation of a novel gene OTP was detected in adjacent             normal tissues even 6 cm away from primary tumors, suggesting that OTP methylation             may qualify as a biomarker for the early detection of breast cancer. In conclusion,             we successfully identified a novel gene OTP frequently methylated in breast cancer             by genome-wide screening. Our results suggest that the OTP gene may play a crucial             role in breast carcinogenesis, although further clinical validation will be needed             to evaluate the potential application of OTP in the early detection of breast             cancer.
authors.affiliation: Genomictree Inc., Daejeon 301-721, Republic of Korea.
authors.forename: Myung Soon
authors.initials: MS
authors.lastname: Kim
authors.forename: Jinsun
authors.initials: J
authors.lastname: Lee
authors.forename: Taejeong
authors.initials: T
authors.lastname: Oh
authors.forename: Youngho
authors.initials: Y
authors.lastname: Moon
authors.forename: Eilsung
authors.initials: E
authors.lastname: Chang
authors.forename: Kwang Sun
authors.initials: KS
authors.lastname: Seo
authors.forename: Benjamin Douglas
authors.initials: BD
authors.lastname: Hoehn
authors.forename: Sungwhan
authors.initials: S
authors.lastname: An
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C489783:LHX2 protein, human; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; C490261:OTP protein, human; D014157:Transcription Factors; D025721:WT1 Proteins