The role of hLHX6-HMR as a methylation biomarker for early diagnosis of cervical cancer.
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.
Jung
Samil
S
Division of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Korea.
Jeong
Dongjun
D
Kim
Jinsun
J
Yi
Lisha
L
Koo
Keunhoe
K
Lee
Jaehyouk
J
Lee
Soon-Duck
SD
Park
Jin-Wha
JW
Chang
Boogi
B
Kim
Chang-Hwan
CH
Kim
Chang-Jin
CJ
Lee
Myeong-Sok
MS
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
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; C121947:LHX6 protein, human; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors