Genetic polymorphisms in the 3'UTR region of the CXCL12 (rs1801157) and TP53 codon 72 (rs1042522) genes may contribute to susceptibility to childhood ALL because they affect some important processes, such as metastasis regulation and tumor suppression.
A substantial number of gastric cancers (31 of 105) showed positive p53 immunostaining without detectable mutations (p53-/IHC+), which suggested an accumulation of wild-type p53 protein, and also a significantly lower risk for metastasis.
The early stages of this disease are asymptomatic and more than 75% of the cases are diagnosed with regional or distant metastases. p53 gene is frequently mutated in some histological subtypes of ovarian carcinomas.
Although there was no association found between expression of hdm2 splicing variants and p53 gene mutations, expression of hdm2 splicing variants was associated with advanced tumor stage (P = .022) and distant metastasis (P = .004) in wild-type p53 cases, and with poor survival of patients (P = .039).
The association of p53 mutation with metastases may explain the poor prognosis reported for HPV negative primary cancers, many of which already contain mutant p53.
In particular, mutations in Kirsten rat sarcoma viral oncogene homolog gene (KRAS), alone or in combination with tumor protein p53 gene (TP53) mutations, were associated with decreased survival probability and with the occurrence of local metastases at recurrence.
The expressions of mutant p53 and ki-67 were examined on tissue microarray containing GIA, adjacent mucosa or adenoma and metastases by immunostaining.
Comparison of primary tumors and their metastases revealed identical results in 88%-90% of the cases, indicating that, in most cases, mutant p53 occurs prior to metastatic spread and remains clonally conserved.
Matched primary and metastasis tissues were evaluated for intragenic mutations in KRAS, CDKN2A, and TP53 and immunolabeled for CDKN2A, TP53, and SMAD4 protein products.
To elucidate how mutant p53 GOF drives metastasis, we developed a traceable somatic osteosarcoma mouse model that is initiated with either a single <i>p53</i> mutation (p53R172H) or <i>p53</i> loss in osteoblasts.
The combined results reveal PGC-1α as a novel "gain-of-function" partner of mutant p53 and indicate that the codon 72 polymorphism influences the impact of mutant p53 on metabolism and metastasis.
TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival.
Tumors with TP53 mutations or with TP53 and TERT promoter mutations were almost always classified as high risk, and the patients developed metastases and/or died of disease.
In addition, we correlated the findings with other relevant molecular markers including the metastasis associated nm23-H1 gene and loss of heterozygosity (LOH) using multiple polymorphic markers for chromosome 17p and sequencing the entire open reading frame (ORF) of the p53 gene.