Prioritizing Gene Cascading Paths to Model Colorectal Cancer Through Engineered Organoids.

ABSTRACT: Engineered organoids by sequential introduction of key mutations could help modeling the dynamic cancer progression. However, it remains difficult to determine gene paths which were sufficient to capture cancer behaviors and to broadly explain cancer mechanisms. Here, as a case study of colorectal cancer (CRC), functional and dynamic characterizations of five types of engineered organoids with different mutation combinations of five driver genes (APC, SMAD4, KRAS, TP53, and PIK3CA) showed that sequential introductions of all five driver mutations could induce enhanced activation of more hallmark signatures, tending to cancer. Comparative analysis of engineered organoids and corresponding CRC tissues revealed sequential introduction of key mutations could continually shorten t

SUBMITTER: Ping Y 

PROVIDER: S-EPMC7010597 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature