Multiple sequential molecular abnormalities in the evolution of human gliomas

Abstract

We have examined a series of 13 benign and 27 malignant human gliomas for evidence of molecular abnormalities of proto-oncogene and putative tumour suppressor gene loci. The results indicated that specific molecular lesions were associated with increasing grades of malignancy. Thus, loss of genetic material on chromosome 17 was present with approximately equal frequency in both benign and malignant gliomas, whereas loss of loci on chromosome 10 was seen only in malignant gliomas. Only the most malignant tumours, known as glioblastoma multiforme, had more than one molecular abnormality in the same tumour. These findings may contribute to our understanding of glial tumour development, as well as improve the accuracy of tumour diagnosis. Images Figure 1 Figure 2 Figure 3

Frequent deletions of material from chromosome arm 1p in oligodendroglial tumors revealed by double‐target fluorescence in situ hybridization and microsatellite analysis

“…Whether this putative suppressor locus is the same as the one implicated in other neuroectodermal tumors remains to be elucidated, but our results lead us to believe that its locus is in lp36. Our data indicating a low incidence of deletions at lp36 in astrocytic tumors and central neurocytomas are compatible with previous reports concerning astrocytomas (James et al, 1988;Venter and Thomas, 1991;Ransom et al, 1992b).…”

p53 protein in low-grade astrocytomas: a study with long-term follow-up

“…This is in keeping with the demonstration that loss of heterozygosity for loci on the short arm of chromosome 17 (17p) (where the p53 gene is located) is shared by cells in each malignancy stage (ElAzouzi et al, 1989;James et al, 1989James et al, , 1990Bigner & Vogelstein, 1990;Venter & Thomas, 1991;Cavenee, 1992;von Diemling et al, 1993). p53 gene and protein alterations could indeed be an early event in tumour progression, which may be associated with clinical aggressiveness.…”

“…Among these parameters are the proliferative activity (Burger et al, 1986;Giangaspero et al, 1987;Hoshino et al, 1988;Allegranza et al, 1991;Jaros et al, 1992), DNA content (Nishizaki et al, 1989) and alterations of oncogenes and tumour-suppressor genes (BaugnetMahieu et al, 1990;Venter & Thomas, 1991;Orian et al, 1992;Jaros et al, 1992;Haapasalo et al, 1993).…”

Genetic versus Histological Grading in Stereotactic Biopsies

“…Molecular genetic analysis o f gliomas has demonstrated allelic deletions, most frequently involving chromosomes 9p, 10, 13, 17p, 19q and 22 [7][8][9], Chro mosome 17 deletions are associated with both low-and high-grade astrocytoma (among other tumors), but chromosome 10 deletions appear to happen exclusive ly in high-grade astrocytoma (grade III and IV according to the W H O classifica tion) and are to be found in 63-72% o f these tumors [8,9], Besides the analysis o f tumor suppressor genes, a search for oncogenes in glioma has revealed epidermal growth factor receptor (EG FR ) gene amplification in highly malignant astrocyto ma [7][8][9]. In particular, all cases with E G F R gene amplification show concomi tant L O H 10 and are to be considered the highest genetic grade o f malignancy [9], Both our results [10,11] and others in genetic grading [12] underscore a signifi cant correlation between L O H 10 ± E G F R gene amplification and a malignant course o f the disease (grade III, IV tumor and survival o f 2-4 months).…”