Innovative Computational Tool Unveils Hidden Cancer DNA Alterations That May Influence Treatment Resistance

Recent advancements in genetic analysis have revealed that some of the most detrimental alterations within cancer DNA are also the most challenging to detect. These structural changes, often located deep within the tumor's genome, can contribute to rapid tumor growth and may undermine the effectiveness of standard diagnostic tests, particularly when tissue samples are limited or degraded. To combat these challenges, researchers at the Mayo Clinic have developed a groundbreaking computational tool named BACDAC. This innovative technology accentuates these elusive genomic patterns by analyzing DNA sequencing data from the entire genome, even in samples that are low in purity or coverage.

The primary goal of BACDAC is to improve the prediction of tumor behavior and assist clinicians in designing more personalized treatment strategies. Central to its approach is the concept of ploidy, which describes the number of complete chromosome sets within a cell. While normal human cells maintain two sets (46 chromosomes), cancer cells frequently exhibit significant gains or losses in chromosome number, disrupting this balance and enabling uncontrolled growth. In a study published in Genome Biology, the research team applied BACDAC to analyze over 650 tumors spanning 12 different cancer types. The analysis successfully identified instances of whole-genome doubling — a phenomenon where a tumor duplicates its entire genetic material — a process often linked to more aggressive tumors and resistance to therapy.

Lead researcher George Vasmatzis, Ph.D., emphasized the significance of BACDAC by stating, "This tool allows us to access an aspect of the genome that has largely remained hidden. Our decades-long understanding of genomic instability now has a practical application through this scalable tool." Additionally, BACDAC offers a visual summary called the Constellation Plot, which provides an intuitive display of whether a tumor's chromosomes are stable or disrupted, aiding researchers and pathologists in interpretation.

The team plans to further validate BACDAC's capabilities and develop it as a clinical diagnostic tool that could significantly influence treatment decisions by unveiling structural genome alterations more clearly. This approach represents a major step forward in leveraging genomic data to understand tumor complexity and resistance mechanisms, ultimately aiming to improve patient outcomes.

Source: https://medicalxpress.com/news/2025-06-tool-exposes-hidden-cancer-dna.html