Droop, A orcid.org/0000-0001-7695-7480, Bruns, A orcid.org/0000-0002-6970-4036, Tanner, G et al. (12 more authors) (2018) How to analyse the spatiotemporal tumour samples needed to investigate cancer evolution: A case study using paired primary and recurrent glioblastoma. International Journal of Cancer, 142 (8). pp. 1620-1626. ISSN 0020-7136
Abstract
Many traits of cancer progression (e.g., development of metastases or resistance to therapy) are facilitated by tumour evolution: Darwinian selection of subclones with distinct genotypes or phenotypes that enable such progression. Characterising these subclones provide an opportunity to develop drugs to better target their specific properties but requires the accurate identification of somatic mutations shared across multiple spatiotemporal tumours from the same patient. Current best practices for calling somatic mutations are optimised for single samples, and risk being too conservative to identify shared mutations with low prevalence in some samples. We reasoned that datasets from multiple matched tumours can be used for mutual validation and thus propose an adapted two‐stage approach: (1) low‐stringency mutation calling to identify mutations shared across samples irrespective of the weight of evidence in a single sample; (2) high‐stringency mutation calling to further characterise mutations present in a single sample. We applied our approach to three‐independent cohorts of paired primary and recurrent glioblastoma tumours, two of which have previously been analysed using existing approaches, and found that it significantly increased the amount of biologically relevant shared somatic mutations identified. We also found that duplicate removal was detrimental when identifying shared somatic mutations. Our approach is also applicable when multiple datasets e.g. DNA and RNA are available for the same tumour.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2017 UICC. This is the peer reviewed version of the following article: Droop, A , Bruns, A, Tanner, G et al. (2017) How to Analyse The Spatiotemporal Tumour Samples Needed To Investigate Cancer Evolution: A Case Study using Paired Primary and Recurrent Glioblastoma. International Journal of Cancer , which has been published in final form at https://doi.org/10.1002/ijc.31184. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
Keywords: | Somatic mutation; Variant calling; Intratumour heterogeneity; Spatiotemporal; Duplicates; Tumour evolution |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Pathology & Tumour Biology (Leeds) |
Funding Information: | Funder Grant number MRC MR/L01629X/1 Wellcome Trust No Ext Ref Given Leeds Teaching Hospitals Charitable Foundation 9R11/14-11 |
Depositing User: | Symplectic Publications |
Date Deposited: | 29 Nov 2017 13:00 |
Last Modified: | 14 Dec 2018 01:38 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/ijc.31184 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:124598 |