Please use this identifier to cite or link to this item: doi:10.22028/D291-29442
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Title: DNA copy number changes define spatial patterns of heterogeneity in colorectal cancer
Author(s): Mamlouk, Soulafa
Childs, Liam Harold
Aust, Daniela
Heim, Daniel
Melching, Friederike
Oliveira, Cristiano
Wolf, Thomas
Durek, Pawel
Schumacher, Dirk
Bläker, Hendrik
von Winterfeld, Moritz
Gastl, Bastian
Möhr, Kerstin
Menne, Andrea
Zeugner, Silke
Redmer, Torben
Lenze, Dido
Tierling, Sascha
Möbs, Markus
Weichert, Wilko
Folprecht, Gunnar
Blanc, Eric
Beule, Dieter
Schäfer, Reinhold
Morkel, Markus
Klauschen, Frederick
Leser, Ulf
Sers, Christine
Language: English
Title: Nature communications
Volume: 8
Issue: 1
Publisher/Platform: Nature Publishing Group
Year of Publication: 2017
Publikation type: Journal Article
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.
DOI of the first publication: 10.1038/ncomms14093
Link to this record: hdl:20.500.11880/27897
ISSN: 2041-1723
Date of registration: 25-Sep-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Professorship: NT - Prof. Dr. Jörn Walter
Collections:Die Universitätsbibliographie

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