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01.06.2016 | original report | Ausgabe 2/2016

memo - Magazine of European Medical Oncology 2/2016

Association of TP53 mutations with TP53 codon 72 polymorphism and outcome in triple-negative breast cancer

Zeitschrift:
memo - Magazine of European Medical Oncology > Ausgabe 2/2016
Autoren:
Mathilde Foedermayr, Miriam Sebesta, Margaretha Rudas, Anna S. Berghoff, Regina Promberger, Matthias Preusser, Peter Dubsky, Michael Gnant, Guenther G. Steger, Ansgar Weltermann, Christoph C. Zielinski, Otto Zach, Rupert Bartsch

Abstract

Despite recent improvements, triple-negative breast cancer (TNBC) remains a breast cancer subtype with poor prognosis. TP53 mutations are commonly associated with TNBC, suggesting a role in breast cancer carcinogenesis. In addition to mutations, several reports focused on TP53 polymorphisms and their association with breast cancer risk and outcome. TP53 codon Pro72Arg polymorphism may predict response to anti-cancer therapy as Pro72 is apparently less effective in the induction of apoptosis.
Here, we investigated a potential association of TP53 mutations with TP53 codon 72 polymorphism and clinical outcome in a homogeneous cohort of TNBC patients.
DNA isolated from formalin-fixed paraffin-embedded tissue of 35 consecutive TNBC patients was investigated for TP53 mutation and TP53 codon 72 polymorphic status by Sanger sequencing.
The kind of TP53 mutations were associated with particular polymorphic Pro72Arg genotypes. Frameshift mutations were significantly correlated with Pro/Pro carriers, nonsense mutations showed a trend for Pro/Arg carriers. Despite this observation no association with clinical outcome was observed.
Further studies with larger and more homogeneous cohorts are warranted in order to elucidate a potential association of TP53 Pro72Arg polymorphism and particular TP53 mutations with TNBC carcinogenesis and outcome.

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