Hypermethylation and loss of heterozygosity of tumor suppressor genes on chromosome 3p in cervical cancer.
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.
Choi
Chel Hun
CH
Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Lee
Kyung-Mee
KM
Choi
Jung-Joo
JJ
Kim
Tae-Joong
TJ
Kim
Woo Young
WY
Lee
Jeong-Won
JW
Lee
Sun-Joo
SJ
Lee
Je-Ho
JH
Bae
Duk-Soo
DS
Kim
Byoung-Gie
BG
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
D017766:Acid Anhydride Hydrolases; D004247:DNA; D017931:DNA Primers; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase