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UK researchers have uncovered key cancer gene mutations that drive tumour growth, offering new insights into cancer development and potential treatments
For the first time, scientists from Manchester and London have decoded the full range of cancer gene mutations driving tumour growth. Their work could lead to more effective treatments for thousands of cancer patients.
The findings are published in Nature Genetics.
Scientists decoded millions of cancer gene mutations
Scientists from the University of Manchester and the Institute of Cancer Research, London, forensically examined the cancer gene mutations in 16 different cancers.
The team used whole-genome sequencing data from nearly 11,000 NHS patients with cancer and is part of Genomics England’s 100,000 Genomes Project, the largest single genomics study for cancer ever undertaken worldwide.
After analysing millions of cancer gene mutations in 11,000 tumours, the researchers identified the most comprehensive map yet of genetics ‘scars’ left behind in cancer DNA.
The researchers catalogued 370 million mutations and assigned them to 134 distinct mutational ‘signatures’. Mutational signatures are specific patterns of DNA changes that help identify the processes driving cancer. Of these, 26 signatures were not previously included in the database of known signatures used by many scientists.
According to the study, many more patients could benefit from precision therapies than previously recognised. Researchers identified homologous recombination deficiency (HRD), a DNA repair defect revealed by specific cancer gene mutations, in 16% of breast and 14% of ovarian tumours, making them sensitive to PARP inhibitors and platinum-based chemotherapy. Over 7,700 UK breast cancer patients and 1,000 ovarian cancer patients might benefit from HRD-targeted treatments, exceeding those identified by standard BRCA1/BRCA2 genetic testing.
Experts reveal how decoding a tumour’s genetic history could improve patient care
Professor David Wedge, professor of cancer genomics and data science at The University of Manchester, said: “Every cancer develops because DNA is damaged over time. Different causes, such as ultraviolet light, tobacco smoke or inherited gene faults, leave different patterns in the genome. By reading these patterns, we can now understand, in a larger proportion of cancers, what caused the cancer, when key mutations occurred, and which treatments are most likely to work.
“Until now, most testing has focused on mutations of a single base (or ‘letter’) in a cancer’s DNA. By analysing the entire genome and examining more complex mutations that affect multiple bases, I hope our research will help improve predictions of which treatments might benefit specific patients. This could enable better targeting of treatment to those patients most likely to benefit, given the genetic make-up of their tumours.”
Professor Richard Houlston, head of cancer genomics at The Institute of Cancer Research, London, said: “The scale of this study was very large, as we analysed samples from almost every tumour type. The quantity of data was enormous, and although laborious to work through, we have been rewarded with a very exciting outcome. This study provides one of the clearest demonstrations yet that reading the full genetic history of a tumour can unlock clues to better patient care. The future of cancer treatment lies not just in finding mutations, but in understanding the story they tell.”
Professor Rob Bristow, Director of the Manchester Cancer Research Centre, a partnership formed in 2006 by The University of Manchester, Cancer Research UK and The Christie NHS Foundation Trust, said: “This remarkable and comprehensive study demonstrates how Manchester is leading the charge in the field of big data genomics. The world-class research coming out of the Wedge lab is pioneering and will transform our understanding of the human genome and the potential for better cancer treatments for our patients.”