Li-Fraumeni syndrome (LFS), caused by the germline mutations in the TP53 gene, leads to significant lifetime risk to cancer in the central nervous system.
Li-Fraumeni and Li-Fraumeni-like (LFS/LFL) Syndrome are cancer predisposition syndromes caused by germline pathogenic variants in TP53 and are associated with an increased risk of multiple early-onset cancers.
Our analysis of cancer genomic databases showed that patients with wild-type RBM10 and p53 survive longer than do those with mutated p53 or less RBM10.
A common facet of these maladies is the transition of a protein from its functional native state into higher order forms, such as oligomers and amyloid fibrils. p53 is an essential tumor suppressor that is prone to such conformational transitions, resulting in its compromised ability to avert cancer.
Resistance to anti-cancer drugs is a major impediment towards efficacious cancer treatment. p53 mutations play an important role in cancer cell resistance to chemotherapeutic drugs.
Taken together, our findings suggest a novel oncogenic function of GRWD1 as a transcriptional regulator of p53 and that GRWD1 might be an attractive therapeutic target and prognostic marker in cancer therapy.
In this Perspective, we provide insight into understanding p53 as a prion-like protein and propose cancer to be recognized as an amyloid or prion-like disease.
TP53 mutation carriers were significantly more likely to have early onset cancer (p < 0.001) and bilateral breast cancer (p = 0.03), they and were significantly more likely to respond to carboplatin-based neoadjuvant chemotherapy compared to anthracycline- or taxane-based regimen in terms of pathologic complete response (50% vs. 0%, p = 0.006).
<i>TP53</i> (tumor protein p53) is a tumor suppressor gene frequently mutated in cancer and implicated in cell-cycle regulation, apoptosis, and angiogenesis.
This enabled successful estimation of TP53 penetrance for three LFS cancer types: breast (BR), sarcoma (SA), and others (OT), from 186 pediatric sarcoma families collected at MD Anderson Cancer Center.
We found that NRF3 promotes tumor growth and malignancy by activating ubiquitin-independent 20S proteasome assembly through inducing the expression of the proteasome maturation protein (POMP) chaperone and thereby degrading the tumor suppressors p53 and Rb.
Notably, no individuals with confirmed germline or likely germline TP53 PVs met classic Li-Fraumeni syndrome (LFS) criteria, only 41% met Chompret LFS criteria, and 59% met neither criteria, based upon provider-reported personal and family cancer history.
Many of these mutations resembled TP53 mutations found in cancer: they impaired protein activity, were predicted to be pathogenic, and clustered in exons 5 to 8 and hotspot codons.
In summary, we provide the first set of penetrance estimates for SPC and MPC for TP53 germline mutation carriers, and demonstrate its accuracy for cancer risk assessment.
Junctional adhesion molecule-A is down-regulated in anaplastic thyroid carcinomas and reduces cancer cell aggressiveness by modulating p53 and GSK3 α/β pathways.