RNA Polymerase II hypertranscription in cancer FFPE samples.

Autor:	Henikoff S; Basic Science Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA., Henikoff JG; Basic Science Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Paranal RM; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Greene JE; Basic Science Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Molecular Medicine and Mechanisms of Disease (M3D) PhD Program, University of Washington, Seattle, WA, USA., Zheng Y; Basic Science Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Russell ZR; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Szulzewsky F; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Kugel S; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Holland EC; Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Ahmad K; Basic Science Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 May 21. Date of Electronic Publication: 2024 May 21.
DOI:	10.1101/2024.02.28.582647
Abstrakt:	Hypertranscription is common in human cancers and predicts poor prognosis. However detection of hypertranscription is indirect, relying on accurately quantifying mRNA levels and estimating cell numbers. Previously, we introduced FFPE-CUTAC, a genome-wide method for mapping RNA Polymerase II (RNAPII) in formalin-fixed paraffin-embedded (FFPE) sections. Here we use FFPE-CUTAC to demonstrate genome-wide hypertranscription both in transgene-driven mouse gliomas and in assorted human tumors at active regulatory elements and replication-coupled histone genes with reduced mitochondrial DNA abundance. FFPE-CUTAC identified RNAPII-bound regulatory elements shared among diverse cancers and readily categorized human tumors despite using very small samples and low sequencing depths. Remarkably, RNAPII FFPE-CUTAC identified de novo and precisely mapped HER2 amplifications punctuated by likely selective sweeps including genes encoding direct positive regulators of RNAPII itself. Our results demonstrate that FFPE-CUTAC measurements of hypertranscription and classifications of tumors using small sections provides an affordable and sensitive genome-wide strategy for personalized medicine. Competing Interests: Declaration of interests S.H. is an inventor in a USPTO patent application filed by the Fred Hutchinson Cancer Center pertaining to CUTAC and FFPE-CUTAC (application number 63/505,964). The remaining authors declare no competing interests.
Databáze:	MEDLINE
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