Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients

被引:84
作者
Chan, MWY
Chan, LW
Tang, NLS
Lo, KW
Tong, JHM
Chan, AWH
Cheung, HY
Wong, WS
Chan, PSF
Lai, FMM
To, KF
机构
[1] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Shatin, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Dept Surg, Shatin, Hong Kong, Peoples R China
[3] Chinese Univ Hong Kong, Dept Chem Pathol, Shatin, Hong Kong, Peoples R China
关键词
RASSF1A; methylation; bladder cancer;
D O I
10.1002/ijc.10971
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
High frequency loss of 3p21.3 region where RASSF1A located was demonstrated in several tumors. We aimed to investigate the methylation status of RASSF1A and the frequency of LOH in 3p21.3 region in bladder cancer. Three bladder cancer cell lines, 40 cases of bladder TCC and 14 cases of paired voided urine samples were subjected to methylation analysis. By methylation specific PCR, complete methylation of promoter region of RASSF1A gene were detected in cell lines T24 and UMUC3. Demethylation treatment re-expressed RASSF1A in these 2 cell lines. Methylation of RASSF1A was also detected in 47.5% (19/40) of the TCC cases but not in 6 carcinoma in situ (CIS) or 6 normal urothelium samples. For LOH study, loss of 3p21.3 region was detected in 57.9% (11/19) of our cases. Interestingly, methylation of RASSF1A was found in 72.7% (8/11) of the cases with LOH but only in 12.5% (1/8) of the cases without LOH. Methylation of RASSF1A was detected in 50% (7/14) of voided urine samples, but not in normal control. It showed a higher sensitivity than conventional urine cytology in detecting cancer cells, especially for low grade cases. In conclusion, our results demonstrated a high frequency of RASSF1A methylation with frequent LOH in 3p21.3 region in bladder cancer. It suggested that it may be a potential tumor suppressor gene in this chromosomal region and can be silenced by promoter hypermethylation. Detection of aberrant gene methylation in routine voided urine was feasible and may provide a non-invasive and sensitive approach for cancer detection. (C) 2003 Wiley-Liss, Inc.
引用
收藏
页码:611 / 616
页数:6
相关论文
共 23 条
  • [1] Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours
    Agathanggelou, A
    Honorio, S
    Macartney, DP
    Martinez, A
    Dallol, A
    Radar, J
    Fullwood, P
    Chauhan, A
    Walker, R
    Shaw, JA
    Hosoe, S
    Lerman, MI
    Minna, JD
    Maher, ER
    Latif, F
    [J]. ONCOGENE, 2001, 20 (12) : 1509 - 1518
  • [2] Baylin SB, 1998, ADV CANCER RES, V72, P141
  • [3] Epigenetic inactivation of RASSF14 in lung and breast cancers and malignant phenotype suppression
    Burbee, DG
    Forgacs, E
    Zöchbauer-Müller, S
    Shivakumar, L
    Fong, K
    Gao, BN
    Randle, D
    Kondo, M
    Virmani, A
    Bader, S
    Sekido, Y
    Latif, F
    Milchgrub, S
    Toyooka, S
    Gazdar, AF
    Lerman, MI
    Zabarovsky, E
    White, M
    Minna, JD
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2001, 93 (09): : 691 - 699
  • [4] Byun DS, 2001, CANCER RES, V61, P7034
  • [5] Chan ASC, 2000, CANCER RES, V60, P5365
  • [6] Chan MWY, 2002, CLIN CANCER RES, V8, P464
  • [7] Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3
    Dammann, R
    Li, C
    Yoon, JH
    Chin, PL
    Bates, S
    Pfeifer, GP
    [J]. NATURE GENETICS, 2000, 25 (03) : 315 - 319
  • [8] The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis
    Dreijerink, K
    Braga, E
    Kuzmin, I
    Geil, L
    Duh, FM
    Angeloni, D
    Zbar, B
    Lerman, MI
    Stanbridge, EJ
    Minna, JD
    Protopopov, A
    Li, JF
    Kashuba, V
    Klein, G
    Zabarovsky, ER
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (13) : 7504 - 7509
  • [9] Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors
    Esteller, M
    Silva, JM
    Dominguez, G
    Bonilla, F
    Matias-Guiu, X
    Lerma, E
    Bussaglia, E
    Prat, J
    Harkes, IC
    Repasky, EA
    Gabrielson, E
    Schutte, M
    Baylin, SB
    Herman, JG
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (07): : 564 - 569
  • [10] Cancer epigenetics comes of age
    Jones, PA
    Laird, PW
    [J]. NATURE GENETICS, 1999, 21 (02) : 163 - 167