ABSTRACT
BACKGROUND: Functional single nucleotide polymorphisms (SNP) in codon 72 of TP53 have been shown to be a risk factor, a prognostic marker, and related factor to age at onset in various cancers. METHODS: We investigated blood samples from 254 patients with glioblastoma and 238 healthy controls. RESULTS: TP53 codon 72 status was not correlated with prognosis and did not differ between glioblastoma and control populations. However, the Pro/Pro genotype was overrepresented in patients <45 years (20.6% vs 6.4% in patients with glioblastoma >45 years, p = 0.002, vs 5.9% in control group, p = 0.001). We then confirmed this result on an independent series of young patients with glioblastoma. Finally, the analysis of tumor DNA found the Pro allele associated with occurrence of TP53 somatic mutation. CONCLUSION: Our data suggest that TP53 functional variation is particularly critical for oncogenesis of glioblastoma in young patients.
Subject(s)
Codon/genetics , Glioblastoma/genetics , Polymorphism, Single Nucleotide/genetics , Tumor Suppressor Protein p53/genetics , Adolescent , Adult , Age Factors , Age of Onset , Aged , Aged, 80 and over , Codon/blood , Female , Follow-Up Studies , Gene Frequency/genetics , Genetic Variation/genetics , Glioblastoma/blood , Glioblastoma/epidemiology , Humans , Male , Middle Aged , Mutation/genetics , Tumor Suppressor Protein p53/blood , Young AdultABSTRACT
We have identified and characterized a novel beta-thalassemic mutation in an Afghanistanifamily. The molecular pathology consists of a single base substitution (TGG-->TAG) at codon 37 of the beta-globin gene, giving rise to a stop codon (TAG). Premature stop of translation results in a truncated protein and usually the phenotype of beta-thalassemia (thal) major in homozygous individuals. However, this was not the case in our proband, who was homozygous for the codon 37 mutation. He presented with the phenotype of thalassemia intermedia with a hemoglobin (Hb) level of 8.1 g/dL and no previous history of blood transfusions. High performance liquid chromatography (HPLC) analysis showed exclusively Hb F except for a Hb A2 level within normal limits. Subsequent analysis demonstrated homozygosity for the XmnI Ggamma polymorphism and heterozygosity for a deletional alpha-thal (alphaalpha/-alpha(-3.7)). These findings might, at least partly, explain the beta-thal intermedia phenotype observed in the proband.
Subject(s)
Codon, Nonsense , Codon/genetics , Globins/genetics , Point Mutation , beta-Thalassemia/genetics , Adult , Afghanistan , Child , Codon/blood , Family , Female , Fetal Hemoglobin/analysis , Globins/analysis , Hemoglobins, Abnormal/analysis , Humans , Male , PhenotypeABSTRACT
Genomic DNA from two Brazilian hemoglobin (Hb) Lepore heterozygotes of Italian ancestry have been studied in order to identify the Hb Lepore type and to sequence the breakpoint region. The two genes were sequenced after PCR amplification and had the delta globin sequence up to exon 2 codon 68 while the first specific base for the beta globin gene was at codon 86 of the second exon; between the two ends, they had 51 base pairs in common with the delta and beta globin genes. These data indicate that the mutation was of the Hb Lepore Baltimore type. The Lepore chromosome haplotype was different from that previously described in members of a Spanish family with Hb Lepore Baltimore. These data suggest that independent mutations have given rise to Hb Lepore Baltimore in different regions of the world.
