Genetic alterations in astrocytic tumors: hints to a molecular epidemiological interpretation.
General incidence of brain tumors has significantly increased over the past two decades. Although the aetiology of this increase has not been determined, increased life span and improved diagnosis methods can partially be responsible for it. Starting from the epidemiological data on risk factors, we reviewed the molecular events known to be involved in the genesis and progression of the most common brain neoplasm in adult, namely astrocytoma. Alterations in different genes, encoding key regulatory elements in the cell cycle control, were reviewed. In light of the molecular epidemiological notion that carcinogens leave fingerprints, point mutations at the p53 locus from a panel of astrocytic tumor patients from all over the world were analysed. The results of this analysis suggest that the majority of astrocytomas may have a spontaneous origin. In particular, the kind of mutational events observed suggests a major role for mutagenic events occurring at CpG sites. In order to yield valid conclusions on the potential role of environmental mutagenic factors, well designed molecular epidemiological studies on populations clearly showing a higher relative risk of developing brain tumors are needed.
Fronza
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Laboratorio di Mutagenesi, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Ottaggio
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Campomenosi
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Abbondandolo
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D000328:Adult; D001254:Astrocytoma / Q000453:epidemiology / Q000235:genetics*; D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018899:CpG Islands; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004782:Environmental Health; D016158:Genes, p53; D005909:Glioblastoma / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008780:Methyltransferases / Q000378:metabolism; D009154:Mutation; D019853:O(6)-Methylguanine-DNA Methyltransferase; D012307:Risk Factors
D004273:DNA, Neoplasm; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D018844:Cyclin-Dependent Kinases