UK researchers have discovered key changes in a cancer gene that drive tumor growth, shedding new light on cancer development and potential treatment.
For the first time, scientists in Manchester and London have identified the full range of cancer genes that drive tumor growth. Their work could lead to more effective treatments for thousands of cancer patients.
The findings were published in Nature Genetics.
Scientists identified millions of cancer genes
Scientists at the University of Manchester and the Center for Cancer Research, London, analyzed cancer gene mutations in 16 different types of cancer.
The team used genome sequencing data from almost 11,000 NHS patients with cancer and are part of Genomics England’s 100,000 Genomes Project, the largest cancer genetic study ever undertaken worldwide.
After analyzing millions of cancer gene mutations in 11,000 tumors, the researchers obtained the most comprehensive map of the remaining genes in cancer DNA.
The researchers cataloged 370 million mutations and assigned them to 134 distinct ‘signatures’. Mutation signatures are unique patterns of DNA changes that help identify mechanisms that drive cancer. Of these, 26 signatures were not included in the database of known signatures used by many scientists.
According to the study, more patients could benefit from more effective treatments than previously known. Researchers identified homologous recombination defects (HRD), a DNA repair defect revealed by certain cancer gene mutations, in 16% of breast and 14% of ovarian tumors, which made them sensitive to PARP inhibitors and platinum-based chemotherapy. More than 7,700 breast cancer patients in the UK and 1,000 ovarian cancer patients could benefit from HRD-targeted therapy, more than those identified by routine BRCA1/BRCA2 genetic testing.
Experts reveal how identifying a tumor’s genetic history could improve patient care
Professor David Wedge, professor of cancer genetics at the University of Manchester, said: “Every cancer arises because DNA is damaged over time.” Various causes, such as ultraviolet light, tobacco smoke or the genes we have inherited, leave different patterns in the genes.
“Until now, most tests have focused on single-base (or ‘letter’) changes in cancer DNA. By analyzing the entire genome and examining complex changes that affect multiple bases, I hope our research will help improve predictions of whether treatment can benefit certain patients.
Professor Richard Houlston, head of cancer genomics at the Center for Cancer Research in London, said: “The scope of this study was very large, as we analyzed samples from every type of tumor. Treatment is not only based on finding changes in genes, but also understanding the story they tell.”
Professor Rob Bristow, Director of the Manchester Cancer Research Centre, a partnership established in 2006 by the University of Manchester, Cancer Research UK and The Christie NHS Foundation Trust, said: “This amazing and comprehensive study shows how Manchester is leading the way in the field of big data genetics.
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