TIPE1 promotes cervical cancer progression by repression of p53 acetylation and is associated with poor cervical cancer outcome

Cervical cancer is the fourth most common malignancy diagnosed in women worldwide. Nearly all cases of cervical cancer result from infection with the human papillomavirus, and the prevention of cervical cancer includes screening and vaccination. Primary treatment options for patients with cervical cancer may include surgery or a concurrent chemoradiotherapy regimen consisting of cisplatin-based chemotherapy with external beam radiotherapy and brachytherapy. Cervical cancer causes more than one quarter of a million deaths per year as a result of grossly deficient treatments in many developing countries. This warrants a concerted global effort to counter the shocking loss of life and suffering that largely goes unreported. This article provides a review of the biology, prevention, and treatment of cervical cancer, and discusses the global cervical cancer crisis and efforts to improve the prevention and treatment of the disease in underdeveloped countries. Cancer 2017. © 2017 American Cancer Society.

A large amount of data is available on the functional impact of missense mutations in TP53 and on mutation patterns in many different cancers. New data on mutant p53 protein function, cancer phenotype and prognosis have recently been integrated in the International Agency for Research on Cancer TP53 database (http://www-p53.iarc.fr/). Based on these data, we summarize here current knowledge on the respective roles of mutagenesis and biological selection of mutations with specific functional characteristic in shaping the patterns and phenotypes of mutations observed in human cancers. The main conclusion is that intrinsic mutagenicity rates, loss of transactivation activities, and to a lesser extent, dominant-negative activities are the main driving forces that determine TP53 mutation patterns and influence tumor phenotype. In contrast, current experimental data on the acquisition of oncogenic activities (gain of function) by p53 mutants are too scarce and heterogenous to assess whether this property has an impact on tumor development and outcome. In the case of inherited TP53 mutations causing Li-Fraumeni and related syndromes, the age at onset of some tumor types is in direct relation with the degree of loss of transactivation capacity of missense mutations. Finally, studies on large case series demonstrate that TP53 mutations are independent markers of bad prognosis in breast and several other cancers, and that the exact type and position of the mutation influences disease outcome. Further studies are needed to determine how TP53 haplotypes or loss of alleles interact with mutations to modulate their impact on cancer development and prognosis.