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

David Sidransky, Tom Mikkelsen, Karl Schwechheimer, Mark L. Rosenblum, Web Cavanee, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

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 tumour pairs. Seven pairs consisted of tumours that were high grade both at presentation and recurrence (group A) and three pairs consisted of low-grade tumours that had progressed to higher grade tumours (group B). In group A pairs, four of the recurrent tumours contained a p53 gene mutation; in three of them, the same mutation was found in the primary tumour. In group B pairs, progression to high grade was associated with a p53 gene mutation. A subpopulation of cells were present in the low-grade tumours that contained the same p53 gene mutation predominant in the cells of the recurrent tumours that had progressed to glioblastoma. Thus, the histological progression of brain tumours was associated with a clonal expansion of cells that had previously acquired a mutation in the p53 gene, endowing them with a selective growth advantage. These experimental observations strongly support Nowell's clonal evolution model of tumour progression4.

Original languageEnglish (US)
Pages (from-to)846-847
Number of pages2
JournalNature
Volume355
Issue number6363
StatePublished - Feb 27 1992

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Sidransky, D., Mikkelsen, T., Schwechheimer, K., Rosenblum, M. L., Cavanee, W., & Vogelstein, B. (1992). Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature, 355(6363), 846-847.