Deciphering genomic dependencies: A systematic exploration of synthetic lethal interactions induced by chromosomal deletions

In this project, we aim to identify synthetic lethal genes associated with chromosomal deletions. To illustrate this, we focused on chromosome 1p, a region frequently deleted in the early stages of liver cancer. After in silico data mining, genes of interest were validated by reverse genetic screens. We created sets of genetic instructions (sgRNAs) to target these genes, introducing them into HCC cells with and without chromosome 1p deletion. After modifying the cells, we performed tests to see how knocking out these genes affected them. Interestingly, we discovered that some HCC cell lines were less affected when we turned off a gene called GPX4, which normally prevents a type of cell death called ferroptosis. This led us to hypothesize that certain liver cancer cell lines might have a reduced vulnerability to ferroptosis, and this could be linked to the specific chromosomal deletions they carry. Our findings suggest a complex relationship between chromosomal deletions and how cells respond to ferroptosis.

Publication History

Article published online:
20 January 2025