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Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution

Baker, A-M; Huang, W; Wang, X-MM; Jansen, M; Ma, X-J; Kim, J; Anderson, CM; ... Graham, TA; + view all (2017) Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution. Nature Communications , 8 , Article 1998. 10.1038/s41467-017-02295-5. Green open access

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Abstract

Intra-tumor heterogeneity (ITH) is a major underlying cause of therapy resistance and disease recurrence, and is a read-out of tumor growth. Current genetic ITH analysis methods do not preserve spatial context and may not detect rare subclones. Here, we address these shortfalls by developing and validating BaseScope—a novel mutation-specific RNA in situ hybridization assay. We target common point mutations in the BRAF, KRAS and PIK3CA oncogenes in archival colorectal cancer samples to precisely map the spatial and morphological context of mutant subclones. Computational modeling suggests that subclones must arise sufficiently early, or carry a considerable fitness advantage, to form large or spatially disparate subclones. Examples of putative treatment-resistant cells isolated in small topographical areas are observed. The BaseScope assay represents a significant technical advance for in situ mutation detection that provides new insight into tumor evolution, and could have ramifications for selecting patients for treatment.

Type: Article
Title: Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-017-02295-5
Publisher version: https://doi.org/10.1038/s41467-017-02295-5
Language: English
Additional information: 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: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, STEM-CELLS, TUMOR EVOLUTION, BREAST-CANCER, CLONAL EXPANSION, HETEROGENEITY, AMPLIFICATION, ADENOMAS, PATTERNS, COLON
UCL classification: UCL > Provost and Vice Provost Offices
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 Pathology
URI: http://discovery.ucl.ac.uk/id/eprint/10046582
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