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The molecular basis for alternative lengthening of telomeres (ALT), a prognostic marker for glioma patients, remains unknown. We examined TP53 status in relation to telomere maintenance mechanism (TMM) in 108 patients with glioblastoma multiforme and two patients with anaplastic astrocytoma from New Zealand and United Kingdom. Tumor samples were analyzed with respect to telomerase activity, telomere length, and ALT-associated promyelocytic leukemia nuclear bodies to determine their TMM. TP53 mutation was analyzed by direct sequencing of coding exons 2 to 11. We found an association between TP53 mutation and ALT mechanism and between wild-type TP53 and telomerase and absence of a known TMM (P < 0.0001). We suggest that TP53 deficiency plays a permissive role in the activation of ALT.

Prediction of recurrence after resection of benign meningiomas represents a significant clinical problem. A prospective study commenced in 1984 aimed to elucidate the molecular mechanisms involved in the development of abnormal karyotype and tumour recurrence in meningiomas. Expression of key cell cycle regulators p53, p21, mdm2 and proliferating cell nuclear antigen (PCNA) were studied by immunohistochemistry in 85 tumours for which follow-up data was available. It was found that most tumours expressed p53, p21 and PCNA, with significant correlations between expression of p53 and both p21 and PCNA. As PCNA fulfils a multifunctional role its expression may be an unreliable indicator of proliferation in benign tumours. The degree of tumour excision remains the best prognostic indicator while p53 is the main predictor of abnormal karyotype. Karyotype is not however, related to prognosis. Incompletely excised tumours which expressed high levels of p53 and p21 did not recur. It is suggested that this is indicative of a fully functional p53-mediated DNA damage response mechanism. Rather than contributing to tumour progression, p53 is fulfilling its role as guardian of the genome in benign meningiomas. This study shows that induction of senescence may be an important tumour suppressor mechanism in benign tumours.

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