ABSTRACT
We screened 50 glioblastomas for P53 mutations. Five glioblastomas showed heterozygous mutations, while three were putatively heterozygous. Six of these eight glioblastomas showed elimination of wild-type P53 mRNA. These results strongly suggest that some sort of mechanism(s) favouring mutated over wild-type P53 mRNA exists in glioblastoma cells with heterozygous mutations of this gene.
Subject(s)
Brain Neoplasms/genetics , Genes, p53 , Glioblastoma/genetics , Mutation , RNA, Messenger/analysis , Tumor Suppressor Protein p53/genetics , Adolescent , Adult , Aged , Female , Humans , Loss of Heterozygosity , Male , Middle Aged , Promoter Regions, GeneticABSTRACT
We described the case of an unusual, complex genetic alteration in 57 year-old male patient with glioblastoma multiforme (GBM) with short survival (6 and half months). Alterations consisted of p53 mutation, LOH 10, LOH 17, LOH 19q and EGFR amplification. LOH1p, LOH 9 and LOH 13 were negative. Immunohistochemical study did not correlate with molecular results. The overexpression of TP53 protein and RB protein was detected only in small percentage of cells and interestingly the overexpression of EGFR was present only focally. Immnunostainings for PTEN, P16, PI3-K were negative. Additionally, we observed an overexpression of IGFB2 protein. This case indicates the accumulation of molecular changes in glioblastoma multiforme in patient with short survival.
Subject(s)
Brain Neoplasms/genetics , Chromosomes, Human, Pair 10 , Chromosomes, Human, Pair 17 , Chromosomes, Human, Pair 19 , ErbB Receptors/genetics , Glioblastoma/genetics , Mutation , Tumor Suppressor Protein p53/genetics , Biomarkers, Tumor/analysis , Brain Neoplasms/chemistry , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Combined Modality Therapy , Fatal Outcome , Gene Amplification , Glioblastoma/chemistry , Glioblastoma/pathology , Glioblastoma/therapy , Humans , Immunoenzyme Techniques , Loss of Heterozygosity , Male , Middle Aged , Mutation, MissenseABSTRACT
The expression of Bcl-2, P53 proteins and known markers of proliferation, namely proliferating cell nuclear antigen (PCNA) and Ki67, in 29 patients with B-cell chronic lymphocytic leukaemia (B-CLL) was investigated. All leukaemic patients were classified, and immunophenotyped by the two-colour immunofluorescence method with the use of fluorocytometry. B-CLL was heterogeneous in the range of biological parameters of tumour cells. B-CLL patients manifested 34% positive Ki67 and 61% PCNA expression, whereas Bcl-2 and P53 positivity was 81% and 42%, respectively. The level of intracellular expression of Bcl-2 and P53 proteins did not depend on the stage of disease estimated by routine methods. Ki67 and PCNA expression was significantly higher in B-CLL patients with more advanced stages of the disease. A statistically significant correlation was established between their mutual expression.
