title: Hypermethylation and loss of heterozygosity of tumor suppressor genes on chromosome 3p in cervical cancer.
abstract: We examined the promoter methylation status and LOH of the chromosome 3p genes, von Hippel-Lindau disease (VHL), retinoic acid receptor beta (RAR-beta), RAS association domain family 1A (RASSF1A), and fragile histidine triad (FHIT), in 37 samples of cervical squamous cell carcinoma and corresponding noncancerous tissues. We also analyzed the expression of RAR-beta protein by immunohistochemistry. Promoter hypermethylation in RAR-beta and FHIT was detected in 41% and 24% of tumors, respectively, whereas, no hypermethylation was detected in the corresponding noncancerous tissues. LOH in the regions of VHL, RAR-beta, RASSF1A, and FHIT was observed in 3%, 30%, 22%, and 10% of informative cases, respectively. There were no correlations between LOH and promoter hypermethylation for all of these genes. Absent immunostaining of RAR-beta protein correlated with hypermethylation and/or LOH of RAR-beta gene. In addition, it correlated with higher level of SCC antigen and more frequent lymph node metastasis. Although biallelic inactivation by hypermethylation and concomitant LOH was infrequent, the high frequency of promoter hypermethylation and/or LOH of RAR-beta and FHIT suggest that they play a role in cervical carcinogenesis independently. In addition, expression of RAR-beta protein might be used as a prognostic factor in this disease.
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Chel Hun
authors.initials: CH
authors.lastname: Choi
authors.forename: Kyung-Mee
authors.initials: KM
authors.lastname: Lee
authors.forename: Jung-Joo
authors.initials: JJ
authors.lastname: Choi
authors.forename: Tae-Joong
authors.initials: TJ
authors.lastname: Kim
authors.forename: Woo Young
authors.initials: WY
authors.lastname: Kim
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Sun-Joo
authors.initials: SJ
authors.lastname: Lee
authors.forename: Je-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Bae
authors.forename: Byoung-Gie
authors.initials: BG
authors.lastname: Kim
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002893:Chromosomes, Human, Pair 3; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008745:Methylation; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D004247:DNA; D017931:DNA Primers; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase