The consequence of oncomorphic TP53 mutations in ovarian cancer

Pavla Brachova; Kristina W Thiel; Kimberly K Leslie

doi:10.3390/ijms140919257

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The consequence of oncomorphic TP53 mutations in ovarian cancer

Journal article

Open access

Peer reviewed

The consequence of oncomorphic TP53 mutations in ovarian cancer

Pavla Brachova, Kristina W Thiel and Kimberly K Leslie

International journal of molecular sciences, Vol.14(9), pp.19257-19275

09/23/2013

DOI: 10.3390/ijms140919257

PMCID: PMC3794832

PMID: 24065105

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Abstract

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.

Ovarian Neoplasms - genetics

Animals

Humans

Ovarian Neoplasms - pathology

Transcriptome

Tumor Suppressor Protein p53 - metabolism

Female

Mutation

Gene Knockout Techniques

Tumor Suppressor Protein p53 - genetics

Details

Title: Subtitle: The consequence of oncomorphic TP53 mutations in ovarian cancer
Creators: Pavla Brachova - Molecular and Cellular Biology Program, University of Iowa, Iowa City, IA 52242, USA. kimberly-leslie@uiowa.edu
Kristina W Thiel
Kimberly K Leslie
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.14(9), pp.19257-19275
DOI: 10.3390/ijms140919257
PMID: 24065105
PMCID: PMC3794832
NLM abbreviation: Int J Mol Sci
ISSN: 1661-6596
eISSN: 1422-0067
Publisher: Switzerland
Grant note: R01 CA099908 / NCI NIH HHS R01CA99908-7 / NCI NIH HHS
Language: English
Date published: 09/23/2013
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9983930272502771

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