Original article
Constitutional p53 mutations associated with brain tumors in young adults

https://doi.org/10.1016/0165-4608(94)00213-UGet rights and content

Abstract

Identification of patients at risk for developing brain tumors is important for the development of preventative strategies. Because individuals with germline p53 mutations may be at increased risk, we examined DNA from brain tumor-derived cell lines and malignant and normal nervous system tissue for p53 gene mutations using the single strand conformation polymorphism assay and direct sequencing of polymerase chain reaction-amplified DNA. We found mutations in the p53 gene in eight of 22 adult glioma tissue specimens and germline mutations in two of these eight patients. In contrast, mutation of the p53 gene was not detectable in either 16 glial tumors occurring in children, glial tumor tissue from three unrelated glioblastoma multiforme patients with a familial history of cancer, or in benign meningiomas. One constitutional p53 mutation was a G to T transversion at codon 154, and the second was a C to T transition at codon 256. Both patients with germline mutations developed glioblastoma multiforme before the age of 31, although the median age for glioma patients is above 50. These findings suggest that p53 germline mutations may identify a subset of young adults predisposed to the development of high-grade astrocytic tumors.

References (61)

  • E. Solomon et al.

    Chromosome aberrations and cancer

    Science

    (1991)
  • C.D. James et al.

    Mitotic recombination of chromosome 17 in astrocytomas

  • M. el-Azouzi et al.

    Loss of distinct regions on the short arm of chromosome 17 associated with tumorigenesis of human astrocytomas

  • D. Fults et al.

    Loss of heterozygosity for loci on chromosome 17p in human malignant astrocytoma

    Cancer Res

    (1989)
  • C. Prives et al.

    The p53 tumor suppressor protein: meeting review

    Genes Dev

    (1993)
  • J.M. Nigro et al.

    Mutations in the p53 gene occur in diverse human tumour types

    Nature

    (1989)
  • M. Hollstein et al.

    p53 mutations in human cancers

    Science

    (1991)
  • L.A. Donehower et al.

    Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours

    Nature

    (1992)
  • M. Harvey et al.

    Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice

    Nat Genet

    (1993)
  • D. Malkin et al.

    Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms

    Science

    (1990)
  • S. Srivastava et al.

    Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome

    Nature

    (1990)
  • F.P. Li et al.

    Rhabdomyosarcoma in children: epidemiologic study and identification of a familial cancer syndrome

    J Natl Cancer Inst

    (1969)
  • D. Malkin et al.

    Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms

    N Engl J Med

    (1992)
  • J. Togochida et al.

    Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma

    N Engl J Med

    (1992)
  • A. Iavarone et al.

    Germ-line and somatic p53 gene mutations in multifocal osteogenic sarcoma

  • D. Sidransky et al.

    Inherited p53 gene mutations in breast cancer

    Cancer Res

    (1992)
  • D. Fults et al.

    p53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression

    Cancer Res

    (1992)
  • R.H. Frankel et al.

    p53 mutations in human malignant gliomas: comparison of loss of heterozygosity with mutation frequency

    Cancer Res

    (1992)
  • A. von Deimling et al.

    p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma

    Cancer Res

    (1992)
  • S. Mashiyama et al.

    Detection of p53 gene mutations in human brain tumors by single-strand conformation polymorphism analysis of polymerase chain reaction products

    Oncogene

    (1991)
  • Cited by (71)

    View all citing articles on Scopus
    View full text