The frequent cytogenetic abnormality--isochromosome 17q [i(17)q]--observed in medulloblastomas (MB) may result in altered expression of the oncosuppressor gene p53 that is located on 17p. p53 expression was therefore evaluated in five MBs and in one MB cell line derived from one of these tumors.
By contrast, only 1 of the 36 patients with AML and no cytogenetic abnormalities of 17p showed a mutation of the P53 gene in exons 5 to 8 (P less than .01).
No losses were found on 12q and 17p despite the fact that the most common cytogenetic abnormality in TGCTs is an i(12p) and that the TP53 gene on 17p is the most frequently mutated gene in human cancers.
The three AFB1-treated cell lines exhibited altered morphologies, chromosome aberrations (numerical and structural aberrations) and loss of the wild-type p53 allele.
We conclude that 1) FISH is a simple and sensitive technique for the detection of numerical and structural chromosome abnormalities; 2) Its application to uncultured samples obviates the alteration of results originated by the probable growth advantage of the normal or neoplastic cell population in vitro; 3) Trisomy 12 appears to define a B-CLL subgroup of atypical morphology; and 4) The p53 deletion is correlated with advanced stage of disease and resistance to treatment.
Our data suggest that in gastric cancer, deletion of 17p is principally responsible for the allelic loss at the p53 gene and that analysis of deletions by the dual-color fluorescence in situ hybridization is a sensitive and useful approach to clarify chromosomal aberrations.
To investigate whether loss of TP53 dependent checkpoints also predisposed the cells to accumulate persistent chromosomal aberrations after DNA damage, cells were exposed to 5 Gy gamma radiation.
The specific pattern of chromosome aberrations suggests the prevalence of an indirect clastogenic effect, determined by the inhibition of p53 regulatory functions on genome stability by BKV TAg.
A human T-acute lymphoblastic leukemia (ALL) cell line (Loucy), derived from cells from a patient with resistant ALL with a t(16:20) and 5q- chromosomal aberrations was evaluated for p53 gene alterations and expression.
In contrast, all mutation-carrying strains showed evidence of genomic instability, expressed as aneuploidy, and accumulated structural chromosome aberrations in up to 100% of cells, usually accompanied by loss of the wild-type TP53 allele, immediately before senescence.
Twenty-two mutations of the N-RAS and TP53 genes were detected, and these mutations were frequently associated with unbalanced chromosomal aberrations.
We did not find concordance between numerical chromosome abnormalities of chromosome 17 and nuclear grading as well as with the immunoexpression of p53 and c-erbB2 studied in the smears.
LCLs derived from R-H subjects retained a significantly higher degree of radiation-induced chromosomal aberrations when compared to normal control LCLs. p53 stabilization by ionizing radiation appeared normal in all but one R-H subject.
These cells retained a p53 wt genotype but presented gross chromosomal aberrations in 15-20% of the analyzed metaphases.The aberrations were not clonal.
We investigated factors of the early recurrence and malignant transformation of histologically benign meningiomas using immunohistochemistry for MIB-1 positive indices (PI) and p53 protein expression, a flow cytometric DNA analysis, and the examination of numerical chromosomal aberrations detected by fluorescence in situ hybridization using an alpha-satellite DNA probe and a bcr gene locus-specific probe.
Studies of Li-Fraumeni syndrome fibroblasts heterozygous for germline TP53 mutations have shown that loss of heterozygosity (LOH) occurs during passaging and is associated with genomic instability, such as chromosomal aberrations and aneuploidy to investigate the genomic changes associated with LOH in Li-Fraumeni (LF) fibroblasts, we have analysed cell strains at increasing population doublings (PD) using Comparative Genomic Hybridization (CGH).
No particular level or pattern of chromosomal anomalies appeared to be associated with p53 status, supporting recent observations that abnormal p53 function is not sufficient to cause chromosomal anomalies in colorectal tumours.
These results suggest that p53 protein abnormalities and chromosomal aberrations may be involved in malignant transformation of endometriosis in the ovary.