P53 MUTATION AND LOSS OF HETEROZYGOSITY ON CHROMOSOME-17 AND CHROMOSOME-10 DURING HUMAN ASTROCYTOMA PROGRESSION

被引:0
|
作者
FULTS, D [1 ]
BROCKMEYER, D [1 ]
TULLOUS, MW [1 ]
PEDONE, CA [1 ]
CAWTHON, RM [1 ]
机构
[1] UNIV UTAH,SCH MED,HOWARD HUGHES MED INST,DEPT HUMAN GENET,SALT LAKE CITY,UT 84132
关键词
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The human brain tumor, astrocytoma, typically progresses through three histopathologically defined stages with the passage of time: one premalignant stage, low-grade astrocytoma; and two malignant stages, anaplastic astrocytoma and glioblastoma multiforme. We correlated the results of a sequence analysis of the tumor suppressor gene, p53, and a restriction fragment length polymorphism analysis of chromosomes 17 and 10 in 45 patients with cerebral astrocytomas at different stages. To detect p53 mutations in tumor DNA, we analyzed polymerase chain reaction products corresponding to every p53-coding exon for single-strand conformation polymorphisms and confirmed the mutations by sequencing. Loss of heterozygosity (LOH) was determined by Southern transfer analysis of somatic and tumor DNA from these same patients using polymorphic markers for various loci on chromosomes 10 and 17. p53 mutations were found in 7 of 25 glioblastomas (28%), in 5 of 14 anaplastic astrocytomas (36%) but in 0 of 6 low-grade astrocytomas. p53 mutations were found in 62% of patients with LOH on chromosome 17p. These results indicated that p53 inactivation is a common genetic event in astrocytoma progression that may signal the transition from benign to malignant tumor stages. LOH on chromosome 10 was found in 61% of glioblastomas, in 23% of anaplastic astrocytomas, but in 0% of low-grade astrocytomas. LOH on chromosome 10 and p53 mutation were found together only in patients with glioblastoma multiforme (22%), suggesting that these genetic changes may accumulate during astrocytoma progression.
引用
收藏
页码:674 / 679
页数:6
相关论文
共 50 条
  • [1] LOSS OF HETEROZYGOSITY ANALYSIS OF CHROMOSOME-9, CHROMOSOME-10 AND CHROMOSOME-17 IN GLIOMAS IN FAMILIES
    WATLING, CJ
    VANMEYEL, DJ
    RAMSAY, DA
    MACDONALD, DR
    CAIRNCROSS, JG
    [J]. CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES, 1995, 22 (01) : 17 - 21
  • [2] LOSS OF HETEROZYGOSITY FOR DNA POLYMORPHISMS MAPPING TO CHROMOSOME-10 AND CHROMOSOME-17 AND PROGNOSIS IN PATIENTS WITH GLIOMAS
    JONES, CE
    DAVIS, MB
    DARLING, JL
    GEDDES, JF
    THOMAS, DGT
    HARDING, AE
    [J]. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1995, 58 (02): : 218 - 221
  • [3] Loss of heterozygosity on chromosome 17 and mutation of the p53 gene in retinoblastoma
    Kato, MV
    Shimizu, T
    Ishizaki, K
    Kaneko, A
    Yandell, DW
    Toguchida, J
    Sasaki, MS
    [J]. CANCER LETTERS, 1996, 106 (01) : 75 - 82
  • [4] P53 mutation, EGFR gene amplification and loss of heterozygosity on chromosome 10, 17 p in human gliomas
    Jin, WX
    Xu, XX
    Yang, TM
    Hua, ZC
    [J]. CHINESE MEDICAL JOURNAL, 2000, 113 (07) : 662 - 666
  • [5] LOSS OF HETEROZYGOSITY ON CHROMOSOME-10 IN HUMAN ASTROCYTOMAS
    DARRAS, BT
    YE, Z
    WU, J
    [J]. ANNALS OF NEUROLOGY, 1991, 30 (03) : 460 - 460
  • [6] HUMAN P53 IS ON THE SHORT ARM OF CHROMOSOME-17
    BENCHIMOL, S
    LAMB, P
    CRAWFORD, L
    SHEER, D
    SOLOMON, E
    SHOWS, T
    BRUNS, G
    PEACOCK, J
    [J]. CYTOGENETICS AND CELL GENETICS, 1985, 40 (1-4): : 580 - 581
  • [7] LOSS OF CONSTITUTIONAL HETEROZYGOSITY IN CHROMOSOME-10 IN HUMAN GLIOBLASTOMA
    WATANABE, K
    NAGAI, M
    WAKAI, S
    ARAI, T
    KAWASHIMA, K
    [J]. ACTA NEUROPATHOLOGICA, 1990, 80 (03) : 251 - 254
  • [8] TOTAL LOSS OF CHROMOSOME-17 AND P53 GENE IN SOLID CANCERS
    HECHT, F
    HECHT, BK
    [J]. CANCER GENETICS AND CYTOGENETICS, 1991, 57 (02) : 229 - 229
  • [9] HUMAN P53 GENE LOCALIZED TO SHORT ARM OF CHROMOSOME-17
    MILLER, C
    MOHANDAS, T
    WOLF, D
    PROKOCIMER, M
    ROTTER, V
    KOEFFLER, HP
    [J]. NATURE, 1986, 319 (6056) : 783 - 784
  • [10] LOSS OF HETEROZYGOSITY ON CHROMOSOME-10 IN HUMAN GLIOBLASTOMA-MULTIFORME
    FUJIMOTO, M
    FULTS, DW
    THOMAS, GA
    NAKAMURA, Y
    HEILBRUN, MP
    WHITE, R
    STORY, JL
    NAYLOR, SL
    KAGANHALLET, KS
    SHERIDAN, PJ
    [J]. GENOMICS, 1989, 4 (02) : 210 - 214