Although mutation or inactivation of the p53 tumor suppressor gene occurs at early stages in gliomas and is associated with tumor progression, many tumors including high-grade glioblastoma multiforme carry a functionally intact p53 gene.
However, the presence of p53 mutations in skin premalignant lesions suggests that these represent early events during tumor progression and additional alterations may be required for SCC development.
Together, these findings suggest that p53 mutations may promote cancer progression by augmenting NFkappaB activation in the context of chronic inflammation.
Several p53 mutant proteins acquire the capability to promote cancer progression and metastasis, a phenomenon defined as Gain of Oncogenic Function (GOF).
This study for the first time provided evidence of p53 alteration through allelic deletion that are common primary somatic mutation events which occur irrespective of grade and stage and are hence probably associated with an early phase of tumorigenesis and/or tumor progression.
At variance with other human malignancies, p53 mutations are not frequent in thyroid cancer and are believed to be responsible mainly for cancer progression to poorly differentiated and aggressive phenotype. p63 and p73, two proteins with a high degree of homology with p53, are overexpressed in thyroid cancer, but their role in cancer initiation or progression is controversial.
Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma.
Such concomitant presence (in carcinomas) or absence (in TGCTs) of DDR activation and DDR aberrations supports the roles of MDC1 and 53BP1 within the ATM/ATR-regulated checkpoint network which, when activated, provides an early anti-cancer barrier the pressure of which selects for DDR defects such as p53 mutations or loss of 53BP1/MDC1 during cancer progression.
The simultaneous inactivation of p53 and INK4a-ARF may be linked to the genetic instability caused by XP and could be advantageous for tumor progression.
These data indicate that in HNSCC, TP53 DNA contact mutations confer a strong selection pressure to eliminate wild-type alleles, and that they result in an accelerated tumour progression and reduced therapeutic responsiveness.
These results support the notion that the development of MM is a multistep process and suggest that alterations in the p53 gene may represent an important late event in MM tumor progression.
These findings strongly suggest that p53 mutation plays a crucial role in the biologically aggressive subtype, and possibly in the process of tumor progression in human chondrosarcoma.
The concomitant expression of oncogenic Kras(G12D) and mutant p53 (Trp53(R172H)) in the murine pancreas results in metastatic PDA that recapitulates the cognate features of human pancreatic cancer providing an excellent animal model to identify genes required for tumor progression.
Dominant-negative (DN) p53 mutations in the tumor suppressor p53 gene partly contribute to human cancer progression by inactivating the remaining wild type allele.
Understanding the mechanisms by which p53 loss and mutation promote tumor metastasis is crucial to understanding the biology of tumor progression and how to appropriately apply targeted therapies.
This suggests that the 245 mutation was particularly important for tumor progression and that there might exist heterogeneity in terms of cancer predisposition potential among the various germline TP53 mutations.
The p53 mutations were found in only metastatic lesion and the only recurrent tumor samples suggesting that the acquisition of p53 mutations may be associated with neoplastic progression.