Breast cancer driver genes found by screening chromosome aberrations in vivo

Scientists reported July 8, 2026, in Nature that screening chromosome-arm alterations in mouse models of basal-like breast cancer identified 90 cancer driver genes. According to Al-Zahrani and colleagues, chromosome instability drives large-scale chromosomal imbalances known as aneuploidies. The team established a CRISPR knockout- and activation-linked assay called CRISPR-KOALA for genetic screens in immunocompetent mouse models of cancer. They compiled the ten most frequent human chromosome-arm-level alterations in basal-like breast cancer, a disease type driven by large copy-number alterations. Using CRISPR-KOALA, they screened the mouse orthologues of 3,752 genes on these arms and identified 90 cancer driver genes. These genes drive distinct signalling pathways including MAPK, HIPPO and WNT. Manipulating the identified cancer driver genes overcomes the need for copy-number alterations in Trp53-mutant basal-like breast cancer mouse models. The study identifies PLGRKT as a potent oncogene on chromosome 9p whose tumour-promoting activity is associated with highly stress-resistant mitochondria and an increased ability to detoxify reactive oxygen species. A Nature Research Briefing states that these instabilities harbour one or two prevalent genes that drive cancer and that bypass the need to accumulate aneuploidies; they also require an intact microenvironment to produce their effects.