While mutation of the P53 tumour suppressor gene is a common feature of many types of cancer, mutational inactivation of P53 in melanoma is uncommon; however, its function often appears abnormal.
Both her benign and malignant lesions showed molecularly identical TP53 mutations, indicating that significant genetic alterations can occur in BBD and supporting the clonal evolution from BBD to malignancy.
To estimate the importance of the DNE of TP53 mutations, we analysed the percentage of cancer cases showing a single heterozygous mutation of TP53 and searched for a cell line with a single heterozygous mutation of this gene.
One germline TP53 mutation (c.408A > T/p.Gln136His) and two somatic mutations (c.1022T > G/p.Phe341Cys and c.108-109ins22/p.His37fsX13) are novel to human cancer.
Further, knockdown of <i>CDC7</i> significantly abrogates mutant p53-driven cancer phenotypes <i>in vitro</i> and <i>in vivo</i> Importantly, high <i>CDC7</i> expression significantly correlates with p53 mutational status and predicts poor clinical outcome in lung adenocarcinoma patients.
The p53 tumor suppressor gene is the most commonly mutated gene in human cancer and is a frequent abnormality in oral squamous cell carcinoma and its precancerous lesions.
Our results indicate that mutational mechanisms, in particular TP53 mutations, are associated with work-related exposure to wood dust in sinonasal cancer.
277Y mutations have been described in human tumours, and Ewing tumour cells expressing this mutant from the endogenous p53 locus selectively activate transcription from transfected luciferase reporters regulated by TTT-mutant p53 binding sites. p53 mutants with altered sequence specificity have potential advantages for cancer gene therapy: if used to activate transcription of conditionally toxic genes they would allow tumour-targeting by p53, which acts as a sensor for the malignant state, but place control over cell killing in the hands of the clinician.
Though p53 codon 72 single-nucleotide polymorphism (SNP) did not affect general cancer risk or age of onset, arginine homozygozity, in contrast to proline homozygozity, was found to decrease breast cancer risk in the later onset sporadic cases.
As part of a study of this phenomenon, we also investigated apoptotic response in a series of breast cancer patients lacking TP53 mutations and in a control group of individuals without cancer.
Recent evidence indicates that some mutations in p53 arise as the cancer progresses from a benign tumor to a metastatic tumor and that these mutations in p53 actively contribute to the process of cancer progression.
TP53 hot spot mutations in ovarian cancer: selective resistance to microtubule stabilizers in vitro and differential survival outcomes from The Cancer Genome Atlas.
There are no data on p53 mutations in esophageal cancer patients from Iran yet; however, this country experiences one of the highest cancer mortality rates in the world for esophageal squamous cell carcinomas (ESCCs).
These results point to the need for further studies aimed at evaluating cancer penetrance modifiers as well as the risk associated between cancer and rare TP53 variants.