A new study by researchers from Fred Hutch Cancer Center and The University of Texas MD Anderson Cancer Center has identified a biomarker that accurately predicts outcomes in meningioma brain tumors and breast cancers. Published in Science, the study highlights a breakthrough in cancer diagnostics.
Scientists discovered that the enzyme RNA Polymerase II (RNAPII) on histone genes correlates with tumor aggressiveness and recurrence. High RNAPII levels indicate excessive cell proliferation and may drive chromosomal changes. This finding introduces a potential diagnostic tool for precision oncology.
OVERCOMING LIMITATIONS IN CANCER ANALYSIS
Traditional RNA sequencing struggles to detect histone RNAs due to their unique structure. The new computational method, developed by Dr. Ye Zheng and colleagues, overcomes this challenge. By integrating a novel experimental approach, researchers successfully analyzed biopsy samples from various cancers, enhancing tumor diagnosis and prognosis.
ADVANCED TECHNOLOGY FOR DECADES-OLD SAMPLES
The study used Cleavage Under Targeted Accessible Chromatin (CUTAC), a profiling technology from Dr. Steven Henikoff’s lab. CUTAC enables high-quality gene expression analysis in formalin-fixed, paraffin-embedded (FFPE) tissue samples, overcoming degradation issues that hinder traditional methods. Researchers found histone gene expression significantly higher in tumor tissues, confirming its role in cancer progression.
HISTONE GENES AND CANCER HYPERTRANSCRIPTION
Histone proteins support DNA structure in chromosomes. Cancercell proliferation demands increased histone production, leading to hypertranscription. Yet, current gene expression analysis often underestimates histone gene activity. The study’s findings suggest histone hypertranscription is a strong indicator of tumor growth.
PREDICTING CANCER OUTCOMES
Researchers tested their hypothesis using CUTAC profiling on 36 FFPE meningioma samples. They integrated this data with nearly 1,300 clinical samples to assess tumor behavior. Elevated RNAPII signals on histone genes reliably distinguished cancerous from normal tissues and accurately predicted tumor recurrence and chromosomal changes. The same method also indicated aggressiveness in breast cancer samples.
IMPLICATIONS FOR CANCER TREATMENT AND DIAGNOSIS
“This technique uncovers a formerly overlooked mechanism of cancer aggressiveness,” said Dr. Henikoff. The study suggests that histone gene activity could serve as a new diagnostic and therapeutic target in oncology.
FUTURE RESEARCH AND VALIDATION
Dr. Zheng’s team plans further validation across multiple cancer types. By refining this approach, researchers hope to develop a non-invasive test to improve early detection and treatment strategies.
The breakthrough study marks a significant step in precision medicine, offering new tools for identifying and treating aggressive ones.
