Researchers from Fred Hutch Cancer Center and The University of Texas MD Anderson Cancer Center have made a significant breakthrough in cancer research, unveiling a biomarker that can reliably predict the aggressiveness of meningioma brain tumors and breast cancers. This discovery, detailed in the journal Science, sheds light on the role of RNA Polymerase II (RNAPII), an enzyme associated with histone genes, in cancer proliferation.

The study highlights that elevated levels of RNAPII on histone genes are indicative of tumor aggressiveness and potential recurrence, suggesting that this genomic technology could serve as a valuable tool in precision oncology. Ye Zheng, an assistant professor specializing in Bioinformatics and Computational Biology, emphasized the significance of histone genes as potential indicators of cancer cell over-proliferation, a factor often overlooked in previous research.

Current RNA sequencing techniques have failed to adequately capture histone RNAs due to their unique structural properties. The innovative approach developed by the research team combines experimental technology with computational analysis, enabling a more comprehensive examination of biopsy samples from diverse cancer types.

Advancements in Biopsy Sample Analysis

A key component of the study was the introduction of a new profiling technology known as Cleavage Under Targeted Accessible Chromatin (CUTAC), which enhances the analysis of gene expression using formalin-fixed, paraffin-embedded (FFPE) samples. These types of samples are routinely preserved for extended periods, but RNA within them can degrade over time, leading to suboptimal data quality.

By focusing on small, fragmented non-coding DNA sequences where RNAPII binds, researchers can directly assess gene transcription activity. Analysis of clinical samples revealed that histone gene expression was markedly higher in tumor samples compared to normal tissues, further supporting the hypothesis that cancer cell proliferation leads to increased histone expression.

Correlation Between RNAPII and Cancer Outcomes

The research team employed CUTAC profiling to analyze 36 FFPE samples from patients suffering from meningioma, a typically benign brain tumor. The findings demonstrated that RNAPII signals on histone genes could effectively differentiate between cancerous and non-cancerous samples. Moreover, these RNAPII signals correlated with clinical grades in meningiomas, accurately predicting rapid recurrence and chromosomal abnormalities.

In a parallel analysis, the technique was applied to breast tumor samples from patients with invasive breast cancer, which also indicated a correlation between RNAPII levels and cancer aggressiveness. Steven Henikoff, a professor at Fred Hutch and co-author of the study, remarked on the potential of this method to reveal underlying mechanisms of cancer behavior and contribute to the development of new diagnostic tests.

The researchers plan to extend their investigations using this technology on FFPE samples from various cancer types to further validate their findings.

Implications for Precision Oncology

This discovery could significantly enhance the ability to assess cancer aggressiveness, offering a promising avenue for developing tailored treatment strategies. By identifying biomarkers that correlate with tumor behavior, oncologists can make more informed decisions regarding patient management and therapeutic approaches.

As the field of oncology continues to evolve, the integration of advanced genomic technologies into clinical practice may lead to improved patient outcomes through more precise and personalized treatment options.