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

Ann-Marie Baker (), Weini Huang, Xiao-Ming Mindy Wang, Marnix Jansen, Xiao-Jun Ma, Jeffrey Kim, Courtney M. Anderson, Xingyong Wu, Liuliu Pan, Nan Su, Yuling Luo, Enric Domingo, Timon Heide, Andrea Sottoriva, Annabelle Lewis, Andrew D. Beggs, Nicholas A. Wright, Manuel Rodriguez-Justo, Emily Park, Ian Tomlinson () and Trevor A. Graham ()
Additional contact information
Ann-Marie Baker: Queen Mary University of London
Weini Huang: Queen Mary University of London
Xiao-Ming Mindy Wang: Advanced Cell Diagnostics
Marnix Jansen: University College London Hospital
Xiao-Jun Ma: Advanced Cell Diagnostics
Jeffrey Kim: Advanced Cell Diagnostics
Courtney M. Anderson: Advanced Cell Diagnostics
Xingyong Wu: Advanced Cell Diagnostics
Liuliu Pan: Advanced Cell Diagnostics
Nan Su: Advanced Cell Diagnostics
Yuling Luo: Advanced Cell Diagnostics
Enric Domingo: University of Oxford
Timon Heide: The Institute of Cancer Research
Andrea Sottoriva: The Institute of Cancer Research
Annabelle Lewis: University of Oxford
Andrew D. Beggs: University of Birmingham
Nicholas A. Wright: Queen Mary University of London
Manuel Rodriguez-Justo: University College London Hospital
Emily Park: Advanced Cell Diagnostics
Ian Tomlinson: University of Birmingham
Trevor A. Graham: Queen Mary University of London

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-02295-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02295-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-02295-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().