Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

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

[thumbnail of 16289oa.pdf]
Preview
PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB

Item Type:Article
Title:DNA copy number changes define spatial patterns of heterogeneity in colorectal cancer
Creators Name:Mamlouk, S., Childs, L.H., Aust, D., Heim, D., Melching, F., Oliveira, C., Wolf, T., Durek, P., Schumacher, D., Blaeker, H., von Winterfeld, M., Gastl, B., Moehr, K., Menne, A., Zeugner, S., Redmer, T., Lenze, D., Tierling, S., Moebs, M., Weichert, W., Folprecht, G., Blanc, E., Beule, D., Schaefer, R., Morkel, M., Klauschen, F., Leser, U. and Sers, C.
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.
Keywords:Adenomatous Polyposis Coli Protein, Colorectal Neoplasms, DNA Copy Number Variations, DNA Mutational Analysis, Fluorescence In Situ Hybridization, Gene Dosage, High-Throughput Nucleotide Sequencing, Mutation, Tumor Suppressor Protein p53, Whole Genome Sequencing
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:8
Page Range:14093
Date:25 January 2017
Official Publication:https://doi.org/10.1038/ncomms14093
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library