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Updated: Jun 29, 2025

Author Spotlight: FISH as a Tool for Precise Gene Amplification Assessment in Cancer Specimens
Published on: July 12, 2024
RNA Polymerase II hypertranscription at histone genes in cancer FFPE samples
Steven Henikoff1,2, Ye Zheng1,3, Ronald M Paranal3
1Basic Science Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Abstract:
Genome-wide hypertranscription is common in human cancer and predicts poor prognosis. To understand how hypertranscription might drive cancer, we applied our FFPE-CUTAC method for mapping RNA Polymerase II (RNAPII) genome-wide in formalin-fixed paraffin-embedded (FFPE) sections. We demonstrate global RNAPII elevations in mouse gliomas and assorted human tumors in small clinical samples and discover regional elevations corresponding to de novo HER2 amplifications punctuated by likely selective sweeps. RNAPII occupancy at replication-coupled histone genes correlated with WHO grade in meningiomas, accurately predicted rapid recurrence, and corresponded to whole-arm chromosome losses. Elevated RNAPII at histone genes in meningiomas and diverse breast cancers is consistent with histone production being rate-limiting for S-phase progression and histone gene hypertranscription driving overproliferation and aneuploidy in cancer, with general implications for precision oncology.
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