FIGURE 4 from Genome-wide CRISPR Screen Reveals RAB10 as a Synthetic Lethal Gene in Colorectal and Pancreatic Cancers Carrying SMAD4 Loss

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posted on 2023-05-04, 14:20 authored by Hélène Erasimus, Vanessa Kolnik, Frédéric Lacroix, Sukhvinder Sidhu, Stéphane D'Agostino, Olivier Lemaitre, Alexandre Rohaut, Isabelle Sanchez, Gilbert Thill, Michel Didier, Laurent Debussche, Christophe Marcireau

Identification of genes required for SMAD4-deficient cells viability via CRISPR/Cas9 viability screen. A, Identification of top candidates. Top 1,000 hits ranked by MAGeCK for each PD0 versus PD15 comparison were compared trough cell lines, as well to an essential list of genes published by Hart and colleagues (2017). A total of 94 genes that were not core-essential genes were found to be essential for the two SMAD4-negative cell lines. B, Heatmap of negative Mageck scores of the four selected top synthetic lethal genes. C, Depleted genes in MIAPaCa-2, DLD1, HT29, and SW620, ranked by their FDR from the MAGeCK analysis. The four top candidate genes are indicated with colored dots.

Funding

Sanofi (Sanofi US)

History

ARTICLE ABSTRACT

This study identified and validated RAB10 as new synthetic lethal gene with SMAD4. This was achieved by conducting a whole-genome CRISPR screens in different colorectal and pancreatic cell lines. A future RAB10 inhibitors could correspond to a new therapeutic solution for patients with cancer with SMAD4 deletion.