The consequence of oncomorphic TP53 mutations in ovarian cancer.
Ovarian cancer is the most lethal gynecological malignancy, with an alarmingly poor prognosis attributed to late detection and chemoresistance. Initially, most tumors respond to chemotherapy but eventually relapse due to the development of drug resistance. Currently, there are no biological markers that can be used to predict patient response to chemotherapy. However, it is clear that mutations in the tumor suppressor gene TP53, which occur in 96% of serous ovarian tumors, alter the core molecular pathways involved in drug response. One subtype of TP53 mutations, widely termed gain-of-function (GOF) mutations, surprisingly converts this protein from a tumor suppressor to an oncogene. We term the resulting change an oncomorphism. In this review, we discuss particular TP53 mutations, including known oncomorphic properties of the resulting mutant p53 proteins. For example, several different oncomorphic mutations have been reported, but each mutation acts in a distinct manner and has a different effect on tumor progression and chemoresistance. An understanding of the pathological pathways altered by each mutation is necessary in order to design appropriate drug interventions for patients suffering from this deadly disease.
Molecular and Cellular Biology Program, University of Iowa, Iowa City, IA 52242, USA. kimberly-leslie@uiowa.edu.
Pavla
P
Brachova
Kristina W
KW
Thiel
Kimberly K
KK
Leslie
D000818:Animals; D005260:Female; D055786:Gene Knockout Techniques; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D016159:Tumor Suppressor Protein p53