In order to investigate possible causes and mechanisms of lung cancer susceptibility differences, the TP53 gene was sequenced in a case-only study of lung cancers (206 men and 103 women).
It was the aim of our study to combine p53 analysis with white-light bronchoscopy (WL) or WL and AF to improve the diagnostic yield in a series of 36 patients with histologically proven lung cancer, pulmonary metastasis or suspected lung cancer.
We examined 52 lung carcinoma cell lines and 106 primary non-small cell lung carcinomas (NSCLC) for mutations in the entire coding region of the p53 gene, from exons 2 to 11.
To be eligible, a study had to deal with p53 assessment in lung cancer (primary site) only, and to provide a survival comparison according to the p53 status.
Rare situations are described with wild type p53 stabilization. p53 mutational spectrum in lung cancer reveals some specificities: 3 hot spot codons (codon 157, 248, 273) are the main target of selective adduct formation from a defined chemical carcinogen of cigarette smoke (BP). p53 stabilized mutants proteins are the targets for immune recognition in patients, leading to secretion of p53 auto-antibodies, and can also elicit T-cell specific cytotoxicity in vitro. p53 was not proven to be of prognostical importance once the tumor has developed.
We previously showed that XPC is predominantly affected by its hypermethylation and is associated with an increased occurrence of p53 mutation in lung cancer.
Several p53-based strategies for treatment of cancer are currently under development. p53 gene therapy has resulted in tumour regression in patients with lung cancer.
Association of allelic imbalance at locus D13S171 (BRCA2) and p53 alterations with tumor kinetics and chromosomal instability (aneuploidy) in nonsmall cell lung carcinoma.
These results indicate that mutation of the p53 tumor suppressor gene plays an important role in the development of primary lung cancer, and that nuclear accumulation of p53 protein is a potential prognostic factor in adenocarcinoma of the lung.
The wild-type form of p53 is dominant over the mutant; thus, restoration of wild-type p53 function in lung cancer cells may suppress their growth as tumors.
The role of high-risk human papillomavius (HPV) 16/18 in the development of lung cancer has recently been explored, and p53 mutation is a finding in lung cancer; however, its association with HPV infection is not well studied.
The widespread presence of a single somatic p53 point mutation in the bronchi of a smoker suggests that a single progenitor bronchial epithelial clone may expand to populate broad areas of the bronchial mucosa-a novel mechanism for field carcinogenesis in the respiratory epithelium that may be of importance in assessing individuals for risk of a second primary tumor as well as in devising effective strategies for chemoprevention of lung cancer.
We conclude that NNK may increase the risk of lung cancer progression and poorer outcomes in patients with p53 mutations by perturbing proper mitotic progression and chromosome integrity.
In contrast to the previous report of biallelic expression of p53 in a case with a germline missense mutation, preferential expression of the wild-type allele was observed in the heterozygous state in both normal lung and peripheral blood lymphocytes of our case, whereas expression of mutant mRNA was readily detectable in her lung cancer in the absence of the remaining wild-type allele.