Absence of mutation of the p73 gene in astrocytic neoplasms

In subgroups of astrocytic neoplasms, including glioblastoma (GBM), mutatio ns of the p53 tumour suppressor,gene lead to loss of growth-suppressive pro perties. A p53-related gene termed p73 has recently been identified; its ge ne product shows structural and functional similarities to p53. After being mapped to chromosome region 1p36, p73 was proposed to act as a tumour supp ressor gene, as this region is frequently deleted in a variety of human can cers, including astrocytic tumours. To determine whether p73 is involved in astrocytoma/GBM development, we analysed 10 pilocytic astrocytomas, 15 WHO grade 11 astrocytomas, 15 WHO grade III anaplastic astrocytomas, and 20 GB M for p73 gene alterations. In parallel, we used six polymorphic markers to determine the allelic status of region 1p36 in this tumour series. Althoug h loss of heterozygosity was evidenced in 12 of 60 cases (20% of samples), PCR-SSCP and direct sequencing failed to detect any gene mutation in the en tire coding region and intronic sequences of p73. Eight tumours displayed f ive distinct polymorphic nucleotide changes, also present in the correspond ing normal DNA. These variations consisted of T -->C variation, with no cha nge in Thr173; C -->T transition, with no change in His197; exon 9 simultan eous double change C -->T and T -->C, with no variations in Ala336 and His3 49, respectively, and C -->T change at exon 9/-24 position of intron 8. The se results suggest that, in astrocytic gliomas, p73 may not play a major ro le as a tumour suppressor, but the relatively high incidence of LOH confirm s the presence at 1p36 of an as yet unidentified gene of this category, wit h a key function in astrocytoma/GBM progression.