New Biomarker Predicts Cancer Outcomes

A groundbreaking study by researchers from Fred Hutch Cancer Center and The University of Texas MD Anderson Cancer Center has unveiled a powerful new biomarker that could revolutionize the prediction of outcomes in meningioma brain tumors and breast cancers.

Advancing Cancer Diagnostics

In a paper published in Science, the team identified a specific enzyme, RNA Polymerase II (RNAPII), found on histone genes as a key indicator of tumor aggressiveness and recurrence. Elevated levels of RNAPII on these genes suggest rapid cancer cell proliferation and potential chromosomal changes, which point to new possibilities in precision oncology.

“It has been overlooked that histone genes could be a rate-limiting factor in cell replication and, in turn, a strong indicator of tumor cell over-proliferation. Current RNA sequencing methods are unable to detect histone RNAs due to their unique structure, leading to underestimation in their presence. Our novel approach, combining a new experimental technology and computational pipeline, establishes a comprehensive ecosystem for enhancing tumor diagnosis and prognosis.”

Ye Zheng, Ph.D., co-first author and assistant professor of Bioinformatics and Computational Biology at MD Anderson

Innovative Technology Reveals New Insights

The study’s findings are made possible by a groundbreaking profiling technology developed by Steven Henikoff, Ph.D., co-first author and professor in the Basic Sciences Division at Fred Hutch. This technology, called Cleavage Under Targeted Accessible Chromatin (CUTAC), improves gene expression studies using formalin-fixed, paraffin-embedded (FFPE) samples, a common storage format for tissue biopsies.

“FFPE samples face degradation over time, leading to lower-quality gene expression data. However, our CUTAC technology allows us to focus on small, fragmented DNA non-coding sequences where RNAPII binds, providing direct measurement of gene transcription activity from the DNA,” explains Dr. Henikoff.

Histone Genes and Cancer Over-Proliferation

Histone proteins are crucial for DNA structure, serving as spools around which DNA strands wrap. The study reveals that current tools for gene expression analysis often overlook histone genes due to their RNA’s unique structure, potentially leading to underestimation of their expression levels in tumors.

The researchers hypothesized that the increased proliferation of cancer cells demands higher levels of histones, leading to hypertranscription of histone genes. By examining clinical samples with the help of CUTAC technology across various cancer types, they confirmed higher histone gene expression in tumor samples compared to normal tissues.

RNAPII Expression as a Predictive Tool

To validate their hypothesis, the team used CUTAC profiling to study 36 FFPE samples from patients with meningioma, a benign brain tumor, and integrated the data with nearly 1,300 publicly available clinical samples and outcomes. RNAPII signals on histone genes reliably distinguished cancer samples from normal ones.

These findings have significant implications for precision oncology, offering a new diagnostic and prognostic tool. Further validation on multiple cancer types is planned to enhance the technology’s utility.

Impact on Cancer Research and Treatment

Beyond meningioma and breast cancers, this discovery has the potential to impact various cancer research areas. The use of this new biomarker could lead to more accurate predictions of cancer aggressiveness and recurrence, guiding clinicians in personalized treatment plans.

With ongoing research supported by institutions like the Howard Hughes Medical Institute and the National Institutes of Health, the future of cancer diagnostics appears promising.

Looking Ahead

The development of this biomarker and profiling technology represents a significant step forward in the fight against cancer. By harnessing information from FFPE samples and leveraging advanced computational methods, researchers can gain deeper insights into cancer biology and improve patient outcomes.

Stay tuned as this groundbreaking research unfolds, and discover how these advancements will shape the future of cancer treatment.

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