Oncotarget

Research Papers:

TP53 mutations determined by targeted NGS in breast cancer: a case-control study

Angeliki Andrikopoulou, Evangelos Terpos, Spyridoula Chatzinikolaou, Kleoniki Apostolidou, Ioannis Ntanasis-Stathopoulos, Maria Gavriatopoulou, Meletios-Athanasios Dimopoulos and Flora Zagouri _

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Oncotarget. 2021. [Epub ahead of print] https://doi.org/10.18632/oncotarget.28071

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Abstract

Angeliki Andrikopoulou1, Evangelos Terpos1, Spyridoula Chatzinikolaou1, Kleoniki Apostolidou1, Ioannis Ntanasis-Stathopoulos1, Maria Gavriatopoulou1, Meletios-Athanasios Dimopoulos1 and Flora Zagouri1

1 Department of Clinical Therapeutics, Alexandra Hospital, Medical School, Athens 11528, Greece

Correspondence to:

Flora Zagouri, email: florazagouri@yahoo.co.uk

Keywords: TP53 mutations; next-generation sequencing; biomarker; prognosis; breast cancer

Received: July 15, 2021     Accepted: August 28, 2021     Published: PUBLISHED_DATE

Copyright: © 2021 Andrikopoulou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Background: Tumor protein 53 (TP53) gene mutations are identified in up to 37% of breast tumors especially in HER-2 positive and basal-like subtype. Previous studies have indicated TP53 mutations as a prognostic biomarker in breast cancer. However, most of these studies performed immunohistochemistry (IHC) for the detection of TP53 mutations.

Aim: The purpose of our study is to evaluate the role of TP53 somatic mutations detected via next-generation sequencing (NGS) as a potential prognostic marker in patients with breast cancer.

Materials and Methods: 82 female patients with Stage I–III breast cancer underwent NGS in paraffin blocks and blood samples during the period 25/09/2019 through 25/05/2021. 23 cases of somatic TP53 mutations and 23 cases of healthy controls were matched on age at diagnosis, menopausal status, histological subtype, histological grade, ki67 expression and disease stage.

Results: Mean age at diagnosis was 52.35 (SD; 11.47) years. The somatic TP53 mutation NM_000546.5:c.824G>A p.(Cys275Tyr) was most frequently detected. Co-existence of PIK3CA mutation was a common finding in somatic TP53-mutant tumors (4/23; 17.4%). Disease-free survival was shorter in TP53-mutated cases (16.3 months vs. 62.9 months). TP53 pathogenic somatic mutations were associated with a 8-fold risk of recurrence in the univariate Cox regression analysis (OR = 8.530, 95% CI: 1.81–40.117; p = 0.007).

Conclusions: Our case-control study suggests that TP53 somatic mutations detected by next-generation sequencing (NGS) are associated with an adverse prognosis in breast cancer.


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