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

Guttery, DS; Blighe, K; Polymeros, K; Paul Symonds, R; Macip, S; Moss, EL; (2018) Racial differences in endometrial cancer molecular portraits in The Cancer Genome Atlas. Oncotarget , 9 (24) pp. 17093-17103. 10.18632/oncotarget.24907. Green open access

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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 reveal ed 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.

Type: Article
Title: Racial differences in endometrial cancer molecular portraits in The Cancer Genome Atlas
Open access status: An open access version is available from UCL Discovery
DOI: 10.18632/oncotarget.24907
Publisher version: https://doi.org/10.18632/oncotarget.24907
Language: English
Additional information: Copyright © Guttery et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited (http://creativecommons.org/licenses/by/3.0/).
Keywords: endometrial cancer; ethnicity; TCGA; somatic copy number aberrations
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10047231
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