Journal Article

DKFZ-2017-01357

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetic subclone architecture of tumor clone-initiating cells in colorectal cancer.

Giessler, K. (First author)DKFZ* ; Kleinheinz, K. (First author)DKFZ* ; Huebschmann, D.DKFZ* ; Balasubramanian, G. P.DKFZ* ; Dubash, T. D.DKFZ* ; Dieter, S. M.DKFZ* ; Siegl, C.DKFZ* ; Herbst, F.DKFZ* ; Weber, S.DKFZ* ; Hoffmann, C. M. ; Fronza, R.DKFZ* ; Buchhalter, I.DKFZ* ; Paramasivam, N.DKFZ* ; Eils, R.DKFZ* ; Schmidt, M.DKFZ* ; von Kalle, C.DKFZ* ; Schneider, M. ; Ulrich, A. ; Scholl, C.DKFZ* ; Fröhling, S.DKFZ* ; Weichert, W.DKFZ* ; Brors, B.DKFZ* ; Schlesner, M.DKFZ* ; Ball, C. R.DKFZ* ; Glimm, H. (Last author)DKFZ*

2017
Rockefeller Univ. Press New York, NY

This record in other databases:  

Please use a persistent id in citations: doi:10.1084/jem.20162017

Abstract: A hierarchically organized cell compartment drives colorectal cancer (CRC) progression. Genetic barcoding allows monitoring of the clonal output of tumorigenic cells without prospective isolation. In this study, we asked whether tumor clone-initiating cells (TcICs) were genetically heterogeneous and whether differences in self-renewal and activation reflected differential kinetics among individual subclones or functional hierarchies within subclones. Monitoring genomic subclone kinetics in three patient tumors and corresponding serial xenografts and spheroids by high-coverage whole-genome sequencing, clustering of genetic aberrations, subclone combinatorics, and mutational signature analysis revealed at least two to four genetic subclones per sample. Long-term growth in serial xenografts and spheroids was driven by multiple genomic subclones with profoundly differing growth dynamics and hence different quantitative contributions over time. Strikingly, genetic barcoding demonstrated stable functional heterogeneity of CRC TcICs during serial xenografting despite near-complete changes in genomic subclone contribution. This demonstrates that functional heterogeneity is, at least frequently, present within genomic subclones and independent of mutational subclone differences.

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Contributing Institute(s):

1. Theoretische Bioinformatik (B080)
2. Translationale Onkologie (G100)
3. Angewandte Bioinformatik (G200)
4. Angewandte Funktionelle Genomik (G102)
5. DKTK Heidelberg (L101)
6. DKTK München (L701)

Research Program(s):

1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2017

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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