p53 mutations are rare events in recurrent cervical cancer

被引:18
作者
Denk, C
Butz, K
Schneider, A
Dürst, M
Hoppe-Seyler, F
机构
[1] Deutsch Krebsforschungszentrum, Angew Tumorvirol, D-69120 Heidelberg, Germany
[2] Univ Jena, Frauenklin, D-07740 Jena, Germany
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 2001年 / 79卷 / 5-6期
关键词
p53; human papillomavirus; cervical cancer; yeast functional assay;
D O I
10.1007/s001090100191
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Mutations of the p53 gene have been shown to be associated with aggressive growth behavior and increased recurrence rates for certain tumors. Primary cervical cancers contain oncogenic human papillomaviruses (HPV) in more than 90% of cases and usually possess wild-type p53 alleles. Cervical cancer cells contain detectable levels of functional p53 protein despite of the expression of the HPV E6 protein, which can induce p53 degradation. Thus, inactivation of p53 by somatic mutation should have functional consequences in HPV-positive cancers. We investigated whether p53 mutations play a role in the recurrence of the disease by analyzing p53 status in 18 biopsy specimens from recurrent cervical cancers. Only one of these (5.6%) contained a p53 mutation, as assessed by a sensitive yeast functional assay that detects mutations of the p53 mRNA between codons 52 and 364. These results indicate that p53 mutations are rare events in recurrent cervical carcinomas, and that somatic mutations of p53 do not provide cervical cancer cells with a selective growth advantage for recurrence.
引用
收藏
页码:283 / 288
页数:6
相关论文
共 40 条
[21]   Activation of p53 in cervical carcinoma cells by small molecules [J].
Hietanen, S ;
Lain, S ;
Krausz, E ;
Blattner, C ;
Lane, DP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (15) :8501-8506
[22]   Alteration of a p53 gene status affects outcome of patients with recurrent ovarian cancer [J].
Irie, T ;
Kigawa, J ;
Minagawa, Y ;
Oishi, T ;
Takahashi, M ;
Shimada, M ;
Kamazawa, S ;
Sato, S ;
Terakawa, N .
ONCOLOGY, 2000, 58 (03) :237-241
[23]   A general primer GP5+/GP6+-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings [J].
Jacobs, MV ;
Snijders, PJF ;
vandenBrule, AJC ;
Helmerhorst, TJM ;
Meijer, CJLM ;
Walboomers, JMM .
JOURNAL OF CLINICAL MICROBIOLOGY, 1997, 35 (03) :791-795
[24]   High frequency of p53 mutations in human oral epithelial dysplasia and primary squamous cell carcinoma detected by yeast functional assay [J].
Kashiwazaki, H ;
Tonoki, H ;
Tada, M ;
Chiba, I ;
Shindoh, M ;
Totsuka, Y ;
Iggo, R ;
Moriuchi, T .
ONCOGENE, 1997, 15 (22) :2667-2674
[25]   A MAMMALIAN-CELL CYCLE CHECKPOINT PATHWAY UTILIZING P53 AND GADD45 IS DEFECTIVE IN ATAXIA-TELANGIECTASIA [J].
KASTAN, MB ;
ZHAN, QM ;
ELDEIRY, WS ;
CARRIER, F ;
JACKS, T ;
WALSH, WV ;
PLUNKETT, BS ;
VOGELSTEIN, B ;
FORNACE, AJ .
CELL, 1992, 71 (04) :587-597
[26]   Tumor-suppressor p53: Implications for tumor development and prognosis [J].
Kirsch, DG ;
Kastan, MB .
JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (09) :3158-3168
[27]   Mutation detection by highly sensitive methods indicates that p53 gene mutations in breast cancer can have important prognostic value [J].
Kovach, JS ;
Hartmann, A ;
Blaszyk, H ;
Cunningham, J ;
Schaid, D ;
Sommer, SS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (03) :1093-1096
[28]   CANCER - P53, GUARDIAN OF THE GENOME [J].
LANE, DP .
NATURE, 1992, 358 (6381) :15-16
[29]   p53, the cellular gatekeeper for growth and division [J].
Levine, AJ .
CELL, 1997, 88 (03) :323-331
[30]   PRESENCE AND PERSISTENCE OF HPV INFECTION AND P53 MUTATION IN CANCER OF THE CERVIX UTERI AND THE VULVA [J].
MILDELANGOSCH, K ;
ALBRECHT, K ;
JORAM, S ;
SCHLECHTE, H ;
GIESSING, M ;
LONING, T .
INTERNATIONAL JOURNAL OF CANCER, 1995, 63 (05) :639-645