Chromosome 10 and 17 deletions and p53 gene mutations in Thai patients with astrocytomas.
The tumor suppressor gene locus is known to be partly responsible for the tumorigenesis of sporadic gliomas, but the genetic events that drive the neoplastic process of this tumor remain largely unknown. We correlated the results of loss of heterozygosity (LOH) analysis on chromosomes 10 and 17 and a point mutation analysis of a tumor suppressor gene, p53, in 21 patients with astrocytomas at different stages. LOH was determined in tumor and leukocyte DNAs of primary human central nervous system tumors. The incidence rate of brain tumors corresponded to every p53-coding exon for single-strand conformation polymorphisms (SSCP) and the mutations were confirmed by sequencing. p53 mutations were found in 2 of 10 glioblastomas (20%) and in 1 of 8 low-grade astrocytomas (12.5%). Similarly, LOH on chromosome 10 was also found in 2 of 10 glioblastomas (20%) and 1 of 8 low-grade astocytomas (12.5%). Neither of the p53 mutations nor LOH on chromosome 10 was observed together in the tumor types analyzed. Interestingly, the p53 mutations were found in 29% of patients with LOH on chromosome 17. The fact that p53 mutation and LOH on chromosome 17 were found together only in glioblastomas, suggested that these genetic changes may accumulate during astrocytoma progression.
Put-Ti-Noi
Supawadee
S
Neuro-Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Bangkok, Thailand.
Petmitr
Songsak
S
Chanyavanich
Voravut
V
Sangruji
Tumtip
T
Theerapuncharoen
Veerasak
V
Hayashi
Kenshi
K
Thangnipon
Wipawan
W
D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics / Q000473:pathology*; D001483:Base Sequence; D002872:Chromosome Deletion; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D013785:Thailand; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53