CRISPR genome editing may select for cells with cancer-associated mutations

Cells with mutations linked to cancer can outcompete normal cells after CRISPR/Cas9 genome editing.

The study, published in Nature, reports that cells with pre-existing mutations known to drive cancer can be positively selected during CRISPR/Cas9 editing. Researchers at Sanford Burnham Prebys, San Diego, California, and the National Cancer Institute (NCI), London, alongside other groups, highlight the importance of monitoring patients undergoing genome editing therapy.

'Our study shows that in many different cell types, CRISPR genome editing can confer a selective advantage to cells harbouring mutations in genes associated with cancer, such as p53 and KRAS,' stated Dr Ani Deshpande, co-senior author and an assistant professor in the NCI-Designated Cancer Centre at Sanford Burnham Prebys. 'We have shown that when CRISPR/Cas9 is used to edit the genome, cells with cancer-associated mutations are likely to be selected to survive – and this is more widespread than scientists previously understood.'

Nearly 1000 human cell lines were analysed after genome editing. In almost every cell type, those with a mutated p53 gene or KRAS oncogene, both known to drive cancer, had a selective advantage and grew faster than normal cells. Previous studies have shown that CRISPR genome editing could lead to the selection of cells with p53 mutations, however this is the first time the effect has been seen in so many diverse cells.

Dr Eytan Ruppin, co-leader of the study and chief of the Cancer Data Science Laboratory at the NCI Centre for Cancer Research, added: 'There are CRISPR therapies being developed to correct mutations in many human tissues, but as others have noted before, we need to proceed with caution, because we may be selecting for cells that carry mutations in key cancer driver genes when using CRISPR/Cas9 editing, and that could be potentially dangerous.'

The research team emphasise the need for patient monitoring during the use of CRISPR-based genome editing therapies, particularly when treating individuals with underlying p53 or KRAS gene mutations.