Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines.

被引:501
作者
Ishii, N
Maier, D
Merlo, A
Tada, M
Sawamura, Y
Diserens, AC
Van Meir, EG
机构
[1] Emory Univ, Dept Neurol Surg, Mol Neurooncol Lab, Atlanta, GA 30332 USA
[2] Emory Univ, Winship Canc Ctr, Atlanta, GA 30332 USA
[3] CHU Vaudois, Dept Neurosurg, Lab Tumor Biol & Genet, CH-1011 Lausanne, Switzerland
[4] Univ Basel Hosp, Dept Res, CH-4031 Basel, Switzerland
[5] Hokkaido Univ, Sch Med, Dept Neurosurg, Sapporo, Hokkaido 060, Japan
关键词
D O I
10.1111/j.1750-3639.1999.tb00536.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
In this study we established the simultaneous status of TP53, p16, p14(ARF) and PTEN tumor suppressor genes in 34 randomly chosen human glioma cell lines. Nine cell lines (26.4%) harbored mutations or deletions in all four tumor suppressor genes and 22 cell lines (64%) had alterations in at least three. Mutations/deletions were found at the following frequencies: TP53(76.5%), p14(ARF) (64.7%), p16 (64,7%), PTEN (73.5%). Thus, there was a high incidence of alterations in the cellular pathways involving the p53 transcription factor (94.1%), the retinoblastoma protein (64.7%) and the PTEN phosphatase (73.5%) and 91% of cell lines carried mutations in two or more pathways, This provides the first clear genetic evidence that these tumor suppressors participate in biological pathways which are functioning separately/independently in glioma cells. The status of the gene alterations did not correlate with tumorigenicity in immunocompromized mice or any clinical parameters, Although the mutation rate was higher in glioma cell lines than that reported for glioma tissues, the alterations were molecularly representative of those found in adult de novo glioblastoma. This study highlights the importance of developing therapeutic approaches applicable to tumors with a broad range of genetic alterations and also provides an invaluable panel of glioma cell lines to make this possible.
引用
收藏
页码:469 / 479
页数:11
相关论文
共 51 条
  • [1] Genetic instability leads to loss of both p53 alleles in a human glioblastoma
    Albertoni, M
    Daub, DM
    Arden, KC
    Viars, CS
    Powell, C
    Van Meir, EG
    [J]. ONCOGENE, 1998, 16 (03) : 321 - 326
  • [2] P53-PROTEIN ACCUMULATION AND GENE-MUTATIONS IN HUMAN GLIOMA CELL-LINES
    ANKER, L
    OHGAKI, H
    LUDEKE, BI
    HERRMANN, HD
    KLEIHUES, P
    WESTPHAL, M
    [J]. INTERNATIONAL JOURNAL OF CANCER, 1993, 55 (06) : 982 - 987
  • [3] ARAP W, 1995, CANCER RES, V55, P1351
  • [4] BIGNER SH, 1990, CANCER RES, V50, P8017
  • [5] BIGNER SH, 1988, CANCER RES, V48, P405
  • [6] MORPHOLOGICAL, IMMUNOCYTOCHEMICAL AND GROWTH-CHARACTERISTICS OF 3 HUMAN GLIOBLASTOMAS ESTABLISHED INVITRO
    BILZER, T
    STAVROU, D
    DAHME, E
    KEIDITSCH, E
    BURRIG, KF
    ANZIL, AP
    WECHSLER, W
    [J]. VIRCHOWS ARCHIV A-PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY, 1991, 418 (04) : 281 - 293
  • [7] Boström J, 1998, CANCER RES, V58, P29
  • [8] Burger P. C., 1993, TUMORS CENTRAL NERVO
  • [9] CONSTITUTIONAL P53 MUTATIONS ASSOCIATED WITH BRAIN-TUMORS IN YOUNG-ADULTS
    CHEN, PC
    IAVARONE, A
    FICK, J
    EDWARDS, M
    PRADOS, M
    ISRAEL, MA
    [J]. CANCER GENETICS AND CYTOGENETICS, 1995, 82 (02) : 106 - 115
  • [10] PTEN/MMAC1 mutations in primary glioblastomas and short-term cultures of malignant gliomas
    Chiariello, E
    Roz, L
    Albarosa, R
    Magnani, I
    Finocchiaro, G
    [J]. ONCOGENE, 1998, 16 (04) : 541 - 545