Direct measurement of RNA Polymerase II hypertranscription in cancer FFPE samples

Henikoff, S.; Henikoff, J. G.; Paranal, R. M.; Greene, J. E.; Russell, Z. R.; Szulzewsky, F.; Kugel, S.; Holland, E. C.; Ahmad, K.

doi:10.1101/2024.02.28.582647

bioRxiv · 10.1101/2024.02.28.582647

Direct measurement of RNA Polymerase II hypertranscription in cancer FFPE samples

Henikoff, S.·Henikoff, J. G.·Paranal, R. M.·Greene, J. E.·Russell, Z. R.·Szulzewsky, F.·Kugel, S.·Holland, E. C.·Ahmad, K.

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Abstract

Genome-wide hypertranscription is common in hu-man cancer and predicts poor prognosis. To under-stand 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 assort-ed human tumors in small clinical samples and discov-er 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, ac-curately 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 aneu-ploidy in cancer, with general implications for precision oncology.

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Henikoff, S., Henikoff, J. G., Paranal, R. M., Greene, J. E., Russell, Z. R., Szulzewsky, F., Kugel, S., Holland, E. C., Ahmad, K.. 2024-03-03. Direct measurement of RNA Polymerase II hypertranscription in cancer FFPE samples. https://doi.org/10.1101/2024.02.28.582647

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