Colorectal Tumor Growth Case Study

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1. A Big Bang model of human colorectal tumor growth
a. The Authors, members of the Curtis Lab at Stanford University, propose and justify the Big Bang model for colorectal tumor growth. This model is dependent on several characteristics found in samples including the absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions. The model concludes that mutations occurring early in the tumor development will have a larger effect on overall tumor composition compared to later mutations in spite of the fitness advantages presented by either mutation. This model also provides a possible biomarker for determination of malignant vs benign phenotypes from the primordial tumor. Carcinomas were …show more content…

The authors. Primarily members of the Sherlock lab at Stanford University, constructed a sequencing-based ultra-high-resolution lineage tracking system in Saccharomyces cerevisiae to allow monitoring of several cell population lineages simultaneously. A plasmid library containing, 500,000 random barcodes was inserted into the genome at a landing pad to act as a barcode. Barcoding requires 48 generations of growth from a common ancestor before analysis. To count the relative frequency of each lineage across time, genomic information including lineage barcodes were isolated from the DNA of pooled populations using a two- step PCR protocol, and sequenced amplicons. The population dynamics observed indicated that for mutations to fixate, they must provide advantages above the mean fitness and grow at a rate quick enough so that mutation establishment is not prevented. This paper served as one of the first primary examples of genetic bar coding, including the methods of inserting genetic barcoding via a restriction enzyme/cloning/ligating mechanism. The articles findings are strong, including theoretical computational models and physical samples analyzed with barcode …show more content…

The authors, members of the Stanford department of medicine, explore the applications of using organoid cultures for cancer modeling purposes. Organoid cultures contain epithelial and mesenchymal components and provide a more accurate multi-lineage cell culture comparable to in vivo systems while also allowing in simple in vitro manipulation techniques. The organoid systems also utilized an air-liquid interface methodology which supports organoid growth as epithelial and mesenchymal hybrids without the necessity for growth factor supplementation and allows in vitro cancer modeling in a “more physiologic milieu” than what was previously possible using transformed cell lines or exclusively epithelial cultures. This has increased utility in an oncology setting due to the ability for is situ histologic observations regarding dysplasia and transformation in an organ context. These results are not found when modeled in standard cell lines, revealing new information about neoplasm growth and development without involving in vivo methods. New developments are exploring the necessities for increased large scale system observations before in vivo or medical trials, and organoid systems are allowing this in a convenient and useful

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