scholarly journals Genetic subclone architecture of tumor clone-initiating cells in colorectal cancer

2017 ◽  
Vol 214 (7) ◽  
pp. 2073-2088 ◽  
Author(s):  
Klara M. Giessler ◽  
Kortine Kleinheinz ◽  
Daniel Huebschmann ◽  
Gnana Prakash Balasubramanian ◽  
Taronish D. Dubash ◽  
...  

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.


2010 ◽  
Author(s):  
Mark C. Hornbrook ◽  
Christopher S. Wendel ◽  
Stephen Joel Coons ◽  
Marcia Grant ◽  
Lisa J. Herrinton ◽  
...  






2003 ◽  
Author(s):  
Dragan Korolija ◽  
Josip Banovic ◽  
Stefan Sauerland ◽  
Snjezana Tadic




Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 246
Author(s):  
Felix C.F. Schmitt ◽  
Martin Schneider ◽  
William Mathejczyk ◽  
Markus A. Weigand ◽  
Jane C. Figueiredo ◽  
...  

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.



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