Oncotarget

Research Papers:

Racial differences in endometrial cancer molecular portraits in The Cancer Genome Atlas

David S. Guttery, Kevin Blighe, Konstantinos Polymeros, R. Paul Symonds, Salvador Macip and Esther L. Moss _

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Oncotarget. 2018; 9:17093-17103. https://doi.org/10.18632/oncotarget.24907

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Abstract

David S. Guttery1,*, Kevin Blighe1,*, Konstantinos Polymeros1,2,3, R. Paul Symonds1, Salvador Macip3 and Esther L. Moss1,2

1Leicester Cancer Research Centre, University of Leicester, Robert Kilpatrick Building, Leicester Royal Infirmary, Leicester, UK

2Department of Gynaecological Oncology, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester, UK

3Mechanisms of Cancer and Ageing Lab, Department of Molecular and Cell Biology, University of Leicester, Leicester, UK

*These authors have contributed equally to this work

Correspondence to:

Esther L. Moss, email: em321@leicester.ac.uk

Keywords: endometrial cancer; ethnicity; TCGA; somatic copy number aberrations

Received: January 15, 2018    Accepted: March 10, 2018    Published: March 30, 2018

ABSTRACT

Endometrial cancer (EC) is now the most prevalent gynaecological malignancy in the Western world. Black or African American women (BoAA) have double the mortality of Caucasian women, and their tumours tend to be of higher grade. Despite these disparities, little is known regarding the mutational landscape of EC between races. Hence, we wished to investigate the molecular features of ECs within The Cancer Genome Atlas (TCGA) dataset by racial groupings. In total 374 Caucasian, 109 BoAA and 20 Asian patients were included in the analysis. Asian women were diagnosed at younger age, 54.2 years versus 64.5 years for Caucasian and 64.9 years for BoAA women (OR 3.432; p=0.011); BoAA women were more likely to have serous type tumors (OR 2.061; p=0.008). No difference in overall survival was evident. The most frequently mutated gene in Caucasian and Asian tumours was PTEN (63% and 85%), unlike BoAA cases where it was TP53 (49%). Mutation and somatic copy number alteration (SCNA) analysis revealed an enrichment of TP53 mutations in BoAAs; whereas POLE and RPL22 mutations were more frequent in Caucasians. Major recurrent SCNA racial differences were observed at chromosomes 3p, 8, 10, and 16, which clustered BoAA tumors into 4 distinct groups and Caucasian tumors into 5 groups. There was a significantly higher frequency of somatic mutations in DNA mismatch repair genes in Asian tumours, in particular PMS2 (p=0.0036). In conclusion, inherent racial disparities appear to be present in the molecular profile of EC, which could have potential implications on clinical management.


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