title: The role of hLHX6-HMR as a methylation biomarker for early diagnosis of cervical cancer.
abstract: The homo sapiens LIM homeobox domain LHX6 gene, hLHX6, is a putative transcription regulator with homeo-domain. Multiple cytosine guanine dinucleotides (CpG island) are found in the genomic sequences between exon 4a and exon 5 of the gene encoding hLHX6s (alternative short iso-form of hLHX6 gene). This specific CpG island, hLHX6-HMR, is found frequently hypermethylated in 7 cervical cancer cell lines as shown in MSP, BSP, and COBRA assays. Methylation densities were also investigated with human tissue samples with a distinctive degree of malignant transformation. Our data showed that the hLHX6-HMR was rarely or partly methylated in the normal and CIN I cells, respectively. In contrast, it was frequently hypermethylated in CIN II, CIN III, and invasive carcinoma cells. In summary, this methylation study led to two conclusions. First, hLHX6-HMR hypermethylation is exclusively associated with cervical carcinogenesis. Second, the epigenetic change in hLHX6-HMR seems to start at CIN I, relatively early stage of cervical cancer development. Therefore, hLHX6-HMR can be used as an effective and sensitive methylation biomarker for early diagnosis of cervical cancer.
authors.affiliation: Division of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Korea.
authors.forename: Samil
authors.initials: S
authors.lastname: Jung
authors.forename: Dongjun
authors.initials: D
authors.lastname: Jeong
authors.forename: Jinsun
authors.initials: J
authors.lastname: Kim
authors.forename: Lisha
authors.initials: L
authors.lastname: Yi
authors.forename: Keunhoe
authors.initials: K
authors.lastname: Koo
authors.forename: Jaehyouk
authors.initials: J
authors.lastname: Lee
authors.forename: Soon-Duck
authors.initials: SD
authors.lastname: Lee
authors.forename: Jin-Wha
authors.initials: JW
authors.lastname: Park
authors.forename: Boogi
authors.initials: B
authors.lastname: Chang
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Kim
authors.forename: Chang-Jin
authors.initials: CJ
authors.lastname: Kim
authors.forename: Myeong-Sok
authors.initials: MS
authors.lastname: Lee
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D042241:Early Diagnosis; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; C121947:LHX6 protein, human; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors