DNA Analysis of NHS Tumors Reveals New Clues About Cancer Causes

In a major advancement in cancer research, scientists analyzing DNA from thousands of NHS patient tumors have uncovered a “treasure trove” of genetic clues that reveal the origins and causes of various cancers. By examining genetic mutations, researchers were able to trace each patient’s unique history of cellular damage and repair, gaining insights into how certain exposures and internal factors contribute to cancer development.

Led by Professor Serena Nik-Zainal from Cambridge University Hospitals and the University of Cambridge, the study analyzed the complete genetic sequences—known as whole-genome sequencing (WGS)—of over 12,000 NHS cancer patients. The research team identified patterns in the DNA, called “mutational signatures,” which act as fingerprints showing whether a cancer may have resulted from environmental exposures like UV light or smoking, or from internal cellular issues.

“With thousands of mutations per cancer, we have unprecedented power to look for commonalities and differences across NHS patients,” said Dr. Andrea Degasperi, a researcher on the team. This extensive dataset allowed the team to uncover 58 previously unknown mutational signatures, hinting at additional, yet-to-be-understood causes of cancer.

According to Professor Nik-Zainal, mutational signatures are like “fingerprints at a crime scene,” which help identify potential causes of cancer. Some of these signatures could guide future treatments, pointing to vulnerabilities, or “Achilles heels,” in certain cancer types that may be targeted with specific drugs.

The study was made possible by the 100,000 Genomes Project, an NHS-led initiative that has collected whole-genome sequences from over 85,000 patients across England. This data enabled researchers to conduct an in-depth “forensic” analysis of NHS cancer genomes, providing valuable insights into how cancer develops in individuals.

The team also developed a tool, FitMS, to help scientists and clinicians identify these mutational signatures in cancer patients. This tool could help tailor treatment plans based on each patient’s unique cancer profile, potentially making cancer management more precise and effective.

Michelle Mitchell, CEO of Cancer Research UK, highlighted the significance of this study: “This study shows how powerful whole genome sequencing tests can be in giving clues into how the cancer may have developed, how it will behave, and what treatment options would work best.”

Professor Matt Brown, chief scientific officer of Genomics England, and Professor Dame Sue Hill, the NHS’s chief scientific officer for England, both emphasized the importance of WGS in improving cancer diagnosis and management. “The NHS contribution to the 100,000 Genomes Project was vital to this research,” said Professor Hill, underlining the great potential of genomic data in healthcare.

To learn more, click here!: https://www.science.org/doi/10.1126/science.abl9283