In this review, we summarize current knowledge about p53 pathway inactivation in childhood blastomas (specifically neuroblastoma, retinoblastoma and Wilms' tumor) through various upstream mechanisms.
We show that (i) in the choroid plexus carcinoma, the germline mutation was detected in a homozygous state due to copy-neutral LOH/uniparental disomy, (ii) in the secondary AML, a complex karyotype led to loss of the wild-type TP53 allele, (iii) in the Wilms tumor, the somatic mutation c.814G>A led to compound heterozygosity.
To assess the impact of TP53 mutations and polymorphisms (PIN2, PIN3, and PEX4) on risk of development, age at diagnosis, and survival in WT, we analyzed 46 blood DNA samples and 31 fresh tumor DNA samples from 52 patients with WT.
Extensive studies have identified somatic mutations at several loci in Wilms' tumorigenesis, including WT1, catenin, Wilms' tumor gene on the X chromosome (WTX) and TP53.
Relationships between survival and the following parameters were studied: tumor cell type, histologic grade, stage, p53 and WT1 expression, TP53 mutation, and presence of associated endometriosis.
In Wilms tumor (WT), mutations in the gene encoding p53, TP53, are correlated with anaplasia; however TP53 variants have not been studied in favorable histology (FH) WTs.
Somatic defects at five loci, WT1, CTNNB1, WTX, TP53 and the imprinted 11p15 region, are implicated in Wilms tumor, the commonest childhood kidney cancer.
The overexpression of p53 in 44 specimens of children (26 boys and 18 girls) with Wilms tumor (median age, 36 months; range, 4 to 96 months) was assessed in Mofid Children's Hospital, Tehran, Iran.
Genes identified as being mutated in Wilms' tumour include TP53, a classic tumour suppressor gene (TSG); CTNNB1 (encoding β-catenin), a classic oncogene; WTX, which accumulating data indicate is a TSG; and WT1, which is inactivated in some Wilms' tumours, similar to a TSG.
Wilms' tumor (WT), the most common pediatric renal malignancy, is associated with mutations in several well-characterized genes, most notably WT1, CTNNB1, WTX, and TP53.
The authors screened the GBM samples for p53 mutation by using PCR and single-stranded conformational polymorphism analysis, and they demonstrated an association between WT1 expression and p53 status.
Wilms tumors are a heterogeneous class of tumors in which Wilms tumor suppressor-1 (WT1) and the p53 tumor suppressor may be variously inactivated by mutation, reduced in expression, or even overexpressed in the wild-type state.
Mutation of p53 has been implicated in progression of classical Wilms tumor (WT) into the anaplastic variant (AWT), drug resistance, and poor prognosis.
A high prevalence of p53 gene mutation and protein expression has been found in the anaplastic variant of Wilms' tumor (WT), known to be associated with poor outcome.