Hyper-Elevated RNA Polymerase II May Point to Increased Tumor Aggressiveness

Researchers from Fred Hutch Cancer Center and MD Anderson Cancer Center have developed a novel technique that directly measures gene transcription activity from DNA, revealing that hyper-elevated levels of RNA Polymerase II (RNAPII) are linked to tumor aggressiveness.

Breakthrough Technology: CUTAC

The new technology—Cleavage Under Targeted Accessible Chromatin (CUTAC)—is specifically designed for formalin-fixed, paraffin-embedded (FFPE) samples, which are widely used in tumor biobanking. Compared to traditional RNA sequencing, CUTAC offers significant advantages:

• Sequences DNA being transcribed by RNAPII before RNA release and processing
• Detects genes expressed at low levels
• Overcomes RNA degradation issues in FFPE samples
• 2-3 times more cost-effective than FFPE-RNA sequencing
• Complete protocol within 1-1.5 days, costing $50-100 per sample

Key Findings

1. Histone genes show consistently high RNAPII signals across multiple cancer types
2. Analysis of 36 noninvasive meningiomas and 13 invasive breast tumors revealed:
   • Strong correlation between histone gene transcription and patient recurrence
   • Reliable distinction between cancer and normal samples using RNAPII enzyme signals
3. Histone gene activity serves as a universal indicator of tumor proliferation rate and recurrence risk

Future Prospects

The technology shows promise for:

• Serving as a powerful tool in precision oncology
• Use in retrospective studies requiring archived tissue samples
• Integration into clinical workflows
• Potential insurance coverage to support personalized treatment decisions

The research team plans further collaborations with clinicians and pathologists to validate the FFPE-CUTAC method across additional cancer types and patient cohorts.

Original Article