Clonal expansion of p53 mutant cells is associated with brain tumour progression

@article{Sidransky1992ClonalEO,
  title={Clonal expansion of p53 mutant cells is associated with brain tumour progression},
  author={David Sidransky and Tom Mikkelsen and Karl Schwechheimer and Mark Rosenblum and Webster K. Cavanee and Bert Vogelstein},
  journal={Nature},
  year={1992},
  volume={355},
  pages={846-847}
}
TUMOUR progression is a fundamental feature of the biology of cancer1. Cancers do not arise de novo in their final form, but begin as small, indolent growths, which gradually acquire characteristics associated with malignancy. In the brain, for example, low-grade tumours (astrocytomas) evolve into faster growing, more dysplastic and invasive high-grade tumours (glioblastomas)2,3. To define the genetic events underlying brain tumour progression, we analysed the p53 gene in ten primary brain… 

Sporadic p53 Mutations and Absence of Ras Mutations in Glioblastomas

No genetic difference could be identified between the primary and the transformed glioblastoma forms as concerns their p53 and ras oncogenes, and there are two possible explanations for these findings.

Recurrent astrocytic tumours - a study of p53 immunoreactivity and malignant progression

The role of p53 in malignant progression of astrocytic tumours is conclusively indicated and a potential role ofp53 LI in predictingmalignant progression at recurrence is suggested.

The effect of p53 gene mutational status, EGFR expression and proliferative potential on clinical outcome in patients with astrocytic glial tumours.

It was clear that tumour grade, age and Ki-67 LI were powerful independent prognostic indicators while the presence of gemistocytes, and alterations of p53 status and over-expression of EGFR were not.

Incidence and timing of p53 mutations during astrocytoma progression in patients with multiple biopsies.

  • K. WatanabeK. Sato H. Ohgaki
  • Medicine, Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1997
This genetic alteration is associated with tumor recurrence but not predictive of progression to a more malignant phenotype, however, the time interval until progression was shorter in patients with low-grade astrocytomas carrying a p53 mutation (P = 0.055).

Mutant, wild type, or overall p53 expression: freedom from clinical progression in tumours of astrocytic lineage

Multivariate analyses revealed that immunohistochemically detected p53 was an independent marker of shortened progression-free and overall actuarial survival in patients with astrocytic tumours, suggesting that increased expression of p53 plays an important role in the pathobiology of these tumours.

A pilot study of recurrence of human glial tumours in light of p53 heterozygosity status

No indicative correlation was found between p53 heterozygosity status on one hand and grade of malignancy (primary and recurrent) and recurrence interval on the other.

Genetic alterations associated with the evolution and progression of astrocytic brain tumours

The observation that somatic p53 mutations in sporadic brain tumours are largely restricted to those of astrocytic origin and thatAstrocytomas also prevail among CNS neoplasms associated with p53 germline mutation strongly suggests, that p 53 mutations are capable of initiating neoplastic transformation in astroCytes of the human nervous system.

Cells with TP53 mutations in low grade astrocytic tumors evolve clonally to malignancy and are an unfavorable prognostic factor

The study indicates that irradiation for WHO grade II astrocytic tumors might be associated with poor outcome and this was independent of TP53 status and these findings have important implications in the clinical management of patients with low grade astocytoma.

Revisiting the role of p53 in primary and secondary glioblastomas.

It is suggested that cytoplasmic p53 may contribute to the formation and maintenance of de novo GBM by virtue of its control of the vasculature of tumors.

THE CLINICAL SIGNIFICANCE OF MUTATIONS OF THE P52 TUMOUR SUPPRESSOR GENE IN HAEMATOLOGICAL MALIGNANCIES

The P53 gene is a tumour suppressor gene situated in 17p13, which has been implicated in the control of apoptosis and the cell cycle, especially at the G1/S transition, and how P53 is inactivated in haematological malignancies is analysed.
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