Read the following abstract: \"Human colorectal tumors bear recurrent mutations
ID: 256719 • Letter: R
Question
Read the following abstract:
"Human colorectal tumors bear recurrent mutations in genes encoding proteins operative in the WNT, MAPK, TGF-b, TP53 and PI3K pathways1,2. Although these pathways influence intestinal stem cell niche signaling3–5, the extent to which mutations in these pathways contribute to human colorectal carcinogenesis remains unclear. Here we use the CRISPR-Cas9 genome-editing system6,7 to introduce multiple such mutations into organoids derived from normal human intestinal epithelium. By modulating the culture conditions to mimic that of the intestinal niche, we selected isogenic organoids harboring mutations in the tumor suppressor genes APC, SMAD4 and TP53, and in the oncogenes KRAS and/or PIK3CA. Organoids engineered to express all five mutations grew independently of niche factors in vitro, and they formed tumors after implantation under the kidney subcapsule in mice. Although they formed micrometastases containing dormant tumor-initiating cells after injection into the spleen of mice, they failed to colonize in the liver. In contrast, engineered organoids derived from chromosome-instable human adenomas formed macrometastatic colonies. These results suggest that ‘driver’ pathway mutations enable stem cell maintenance in the hostile tumor microenvironment, but that additional molecular lesions are required for invasive behavior."
Write an in depth question (Do not answer it) to the author of the abstract relating to the subject matter. The question must be open ended.
Explanation / Answer
please elaborate about the previous research carried out in this field for studying these pathways. What other genome editing methods could have been used? Why would you suggest that crispr is the best possible genome editing method in this case How were the culture conditions modulated. How were the driver pathways identified
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