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KMID : 1137020080190020117
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Journal of Gynecologic Oncology
2008 Volume.19 No. 2 p.117 ~ p.122
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Original Article : Role of 5`-CpG island hypermethylation of the FHIT gene in cervical carcinoma
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Ki Kyung-Do
Lee Sun-Kyung
Tong Seo-Yun
Lee Jong-Min
Song Dong-Hwa
Chi Sung-Gil
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Abstract
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Objectives: The abnormal expression of fragile histidine triad (FHIT) gene has been frequently reported in a variety of epithelial malignancies including cervical carcinoma. Furthermore, in a recent study it was proposed that
transcriptional inactivation of FHIT, as a consequence of aberrant 5’-CpG island methylation, plays an important role
in the carcinogenesis of human cervical carcinoma. The authors sought to determine whether abnormal FHIT transcription occurs in human cervical carcinoma, and if so, whether this abnormal expression is associated with aberrant 5’-CpG island methylation. In addition, the clinical significance of FHIT inactivation was investigated in Korean women with cervical cancer.
Methods: To examine for abnormal transcripts of the FHIT gene, quantitative RT-PCR, genomic DNA-PCR and
nonisotopic RT-PCR-SSCP analysis were performed using the standard method. The methylation status was
determined by methylation specific PCR and bisulfite DNA sequencing.
Results: The FHIT gene was down-regulated in 15 of 58 (25.9%) cervical carcinomas. FHIT promoter hypermethylation was detected in 15 of 15 (100%) abnormally expression in cervical carcinomas. Bisulfite DNA sequencing
confirmed these findings and a significant correlation was found between CpG site hypermethylation and low FHIT
expression. However, no significant correlation was found between reduced FHIT expression and clinicopathological
characteristics.
Conclusion: In this study, FHIT inactivation in cervical cancer was found to be strongly correlated with 5’-CpG island hypermethylation rather than a genetic alteration. Furthermore, no significant relation was found between a lack of
FHIT expression and the prognostic factors of cervical cancer in our Korean cohort.
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KEYWORD
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Cervical carcinoma, FHIT gene, Hypermethylation, Bisulfite-DNA sequencing
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