DNA copy number changes define spatial patterns of heterogeneity in colorectal cancer

Soulafa Mamlouk, Liam Harold Childs, Daniela Aust, Daniel Heim, Friederike Melching, Cristiano Oliveira, Thomas Wolf, Pawel Durek, Dirk Schumacher, Hendrik Bläker, Moritz von Winterfeld, Bastian Gastl, Kerstin Möhr, Andrea Menne, Silke Zeugner, Torben Redmer, Dido Lenze, Sascha Tierling, Markus Möbs, Wilko Weichert, Gunnar Folprecht, Eric Blanc, Dieter Beule, Reinhold Schäfer, Markus Morkel, Frederick Klauschen, Ulf Leser and Christine Sers ()
Additional contact information
Soulafa Mamlouk: Institute of Pathology, Charité Universitätsmedizin Berlin
Liam Harold Childs: Knowledge Management in Bioinformatics, Humboldt University of Berlin
Daniela Aust: German Cancer Consortium (DKTK)
Daniel Heim: Institute of Pathology, Charité Universitätsmedizin Berlin
Friederike Melching: Institute of Pathology, Charité Universitätsmedizin Berlin
Cristiano Oliveira: Institute of Pathology, University of Heidelberg
Thomas Wolf: German Cancer Consortium (DKTK)
Pawel Durek: Experimental Rheumatology, German Rheumatism Research Centre
Dirk Schumacher: Institute of Pathology, Charité Universitätsmedizin Berlin
Hendrik Bläker: Institute of Pathology, Charité Universitätsmedizin Berlin
Moritz von Winterfeld: Institute of Pathology, Charité Universitätsmedizin Berlin
Bastian Gastl: Institute of Pathology, Charité Universitätsmedizin Berlin
Kerstin Möhr: Institute of Pathology, Charité Universitätsmedizin Berlin
Andrea Menne: Institute of Pathology, Charité Universitätsmedizin Berlin
Silke Zeugner: Institute for Pathology, University Hospital Carl Gustav Carus, Technische Universität Dresden
Torben Redmer: Institute of Pathology, Charité Universitätsmedizin Berlin
Dido Lenze: Institute of Pathology, Charité Universitätsmedizin Berlin
Sascha Tierling: FR8.3 Life Sciences, Saarland University
Markus Möbs: Institute of Pathology, Charité Universitätsmedizin Berlin
Wilko Weichert: German Cancer Consortium (DKTK)
Gunnar Folprecht: University Hospital Carl Gustav Carus, University Cancer Center/Medical Dpt. I
Eric Blanc: Core Unit Bioinformatics, Berlin Institute of Health
Dieter Beule: Core Unit Bioinformatics, Berlin Institute of Health
Reinhold Schäfer: Institute of Pathology, Charité Universitätsmedizin Berlin
Markus Morkel: Institute of Pathology, Charité Universitätsmedizin Berlin
Frederick Klauschen: Institute of Pathology, Charité Universitätsmedizin Berlin
Ulf Leser: Knowledge Management in Bioinformatics, Humboldt University of Berlin
Christine Sers: Institute of Pathology, Charité Universitätsmedizin Berlin

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Genetic heterogeneity between and within tumours is a major factor determining cancer progression and therapy response. Here we examined DNA sequence and DNA copy-number heterogeneity in colorectal cancer (CRC) by targeted high-depth sequencing of 100 most frequently altered genes. In 97 samples, with primary tumours and matched metastases from 27 patients, we observe inter-tumour concordance for coding mutations; in contrast, gene copy numbers are highly discordant between primary tumours and metastases as validated by fluorescent in situ hybridization. To further investigate intra-tumour heterogeneity, we dissected a single tumour into 68 spatially defined samples and sequenced them separately. We identify evenly distributed coding mutations in APC and TP53 in all tumour areas, yet highly variable gene copy numbers in numerous genes. 3D morpho-molecular reconstruction reveals two clusters with divergent copy number aberrations along the proximal–distal axis indicating that DNA copy number variations are a major source of tumour heterogeneity in CRC.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms14093 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_ncomms14093

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

DOI: 10.1038/ncomms14093

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 ().