Cancer often exhibits genome-wide hypertranscription, but the mechanisms driving this phenomenon remain unclear. To understand how increased transcription might contribute to cancer progression, Henikoff et al. investigated RNA polymerase II (RNAPII) activity across different tumor types. Mapping RNAPII activity across the whole genome in tumor and normal tissues, the authors found widespread transcriptional changes. They also discovered that RNAPII occupancy at histone genes correlated with tumor aggressiveness, particularly in meningiomas and breast cancers. Elevated RNAPII at histone genes predicted rapid cancer recurrence and corresponded to chromosome losses, suggesting that histone gene hypertranscription may drive overproliferation and genomic instability in cancer. —Di Jiang
