p53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression.

摘要: The human brain tumor, astrocytoma, typically progresses through three histopathologically defined stages with the passage of time: one premalignant stage, low-grade astrocytoma; and two malignant stages, anaplastic astrocytoma glioblastoma multiforme. We correlated results a sequence analysis tumor suppressor gene, p53, restriction fragment length polymorphism chromosomes 17 10 in 45 patients cerebral astrocytomas at different stages. To detect p53 mutations DNA, we analyzed polymerase chain reaction products corresponding to every p53-coding exon for single-strand conformation polymorphisms confirmed by sequencing. Loss heterozygosity (LOH) was determined Southern transfer somatic DNA from these same using polymorphic markers various loci on 17. were found 7 25 glioblastomas (28%), 5 14 (36%) but 0 6 astrocytomas. 62% LOH chromosome 17p. These indicated that inactivation is common genetic event progression may signal transition benign 61% glioblastomas, 23% astrocytomas, 0% mutation together only multiforme (22%), suggesting changes accumulate during progression.