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Germline ancestry influences the evolutionary disease course in lung adenocarcinomas

Schenk, A; López, S; Kschischo, M; McGranahan, N; (2020) Germline ancestry influences the evolutionary disease course in lung adenocarcinomas. Evolutionary Applications 10.1111/eva.12964. Green open access

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Abstract

Evolutionary Applications published by John Wiley & Sons Ltd Precision medicine relies on targeting specific somatic alterations present in a patient's tumor. However, the extent to which germline ancestry may influence the somatic burden of disease has received little attention. We estimated the genetic ancestry of non-small-cell lung cancer (NSCLC) patients and performed an in-depth analysis of the influence of genetic ancestry on the evolutionary disease course. Compared with European Americans (EA), African Americans (AA) with lung adenocarcinoma (LUAD) were found to be significantly younger and smoke significantly less. However, LUADs from AAs exhibited a significantly higher somatic mutation burden, with a more pronounced tobacco carcinogen footprint and increased frequencies of alterations affecting cancer genes. Conversely, no significant differences were observed between lung squamous cell carcinomas (LUSC) from EAs and AAs. Our results suggest germline ancestry influences the somatic evolution of LUAD but not LUSC.

Type: Article
Title: Germline ancestry influences the evolutionary disease course in lung adenocarcinomas
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/eva.12964
Publisher version: http://dx.doi.org/10.1111/eva.12964
Language: English
Additional information: © 2020 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: cancer, genomics, germline ancestry, somatic evolution
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 Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10096781
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