TY - JOUR
T1 - Hypermethylation and loss of heterozygosity of tumor suppressor genes on chromosome 3p in cervical cancer
AU - Choi, Chel Hun
AU - Lee, Kyung Mee
AU - Choi, Jung Joo
AU - Kim, Tae Joong
AU - Kim, Woo Young
AU - Lee, Jeong Won
AU - Lee, Sun Joo
AU - Lee, Je Ho
AU - Bae, Duk Soo
AU - Kim, Byoung Gie
PY - 2007/9/18
Y1 - 2007/9/18
N2 - We examined the promoter methylation status and LOH of the chromosome 3p genes, von Hippel-Lindau disease (VHL), retinoic acid receptor β (RAR-β), 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-β protein by immunohistochemistry. Promoter hypermethylation in RAR-β 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-β, 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-β protein correlated with hypermethylation and/or LOH of RAR-β 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-β and FHIT suggest that they play a role in cervical carcinogenesis independently. In addition, expression of RAR-β protein might be used as a prognostic factor in this disease.
AB - We examined the promoter methylation status and LOH of the chromosome 3p genes, von Hippel-Lindau disease (VHL), retinoic acid receptor β (RAR-β), 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-β protein by immunohistochemistry. Promoter hypermethylation in RAR-β 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-β, 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-β protein correlated with hypermethylation and/or LOH of RAR-β 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-β and FHIT suggest that they play a role in cervical carcinogenesis independently. In addition, expression of RAR-β protein might be used as a prognostic factor in this disease.
KW - Cervical squamous cell carcinoma
KW - Loss of heterozygosity
KW - Promoter hypermethylation
KW - Tumor suppressor genes
UR - https://www.scopus.com/pages/publications/34547670512
U2 - 10.1016/j.canlet.2007.03.015
DO - 10.1016/j.canlet.2007.03.015
M3 - Article
C2 - 17467893
AN - SCOPUS:34547670512
SN - 0304-3835
VL - 255
SP - 26
EP - 33
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -
