Gellert, P;
Segal, CV;
Gao, Q;
López-Knowles, E;
Martin, L-A;
Dodson, A;
Li, T;
... Donnelly, P; + view all
(2016)
Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation.
Nature Communications
, 7
, Article 13294. 10.1038/ncomms13294.
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Abstract
Pre-surgical studies allow study of the relationship between mutations and response of oestrogen receptor-positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 controls). In poor responders (based on Ki67 change), we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores occur in ∼30% of tumours. In phase II, we combine targeted sequencing on another 28 treated patients with phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy.
| Type: | Article |
|---|---|
| Title: | Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ncomms13294 |
| Publisher version: | http://dx.doi.org/10.1038/ncomms13294 |
| Language: | English |
| Additional information: | © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Breast cancer; Cancer genomics; Cancer therapeutic resistance |
| 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 > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1529235 |
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