Groundbreaking study uncovers thousands of cancer-causing genetic variants

HINXTON, United Kingdom — In a landmark discovery, scientists have identified over 5,000 genetic variants that enable certain cancers to thrive, potentially revolutionizing cancer diagnosis and treatment. This groundbreaking research, published in Nature Genetics, not only sheds light on the complex world of cancer genetics but also uncovers a promising new therapeutic target that could slow or even prevent cancer development.

Researchers from the Wellcome Sanger Institute, in collaboration with The Institute of Cancer Research and the University of Cambridge, have conducted an exhaustive analysis of the BAP1 gene, a crucial “tumor protection” gene. Their findings reveal that approximately one-fifth of all possible changes to this gene are pathogenic, significantly increasing the risk of developing cancers of the eye, lung lining, brain, skin, and kidney.

This study stands out not only for its large scale but also for its potential immediate impact on patient care. The results are freely available, allowing doctors around the globe to utilize this information for more accurate diagnoses and tailored treatment plans. Importantly, the study’s inclusive approach benefits individuals from diverse ethnic backgrounds, addressing a long-standing gap in genetics research.

 “Previous approaches for studying how variants affect function in genes have been on a very small scale, or exclude important contexts that may contribute to how they behave. Our approach provides a true picture of gene behavior, enabling larger and more complex studies of genetic variation. This opens up new possibilities for understanding how these changes drive disease,” says Dr. Andrew Waters, first author of the study at the Wellcome Sanger Institute, in a media release.

Methodology: Mapping the Genetic Landscape

The researchers employed an innovative technique called “saturation genome editing” to test all 18,108 possible DNA changes in the BAP1 gene. This method involved artificially altering the genetic code of human cells grown in laboratory dishes, providing a comprehensive view of how different genetic variants affect the gene’s function.

To validate their findings, the team analyzed data from the UK Biobank, comparing the cancer rates of individuals carrying harmful BAP1 variants to those of the general population. This multi-faceted approach allowed for a thorough examination of the gene’s role in cancer development and progression.

Key Results: A New Understanding of Cancer Risk

The study identified 5,665 harmful genetic changes that disrupt the protective effects of the BAP1 protein. Analysis of UK Biobank data confirmed that individuals carrying these harmful variants are over 10% more likely to be diagnosed with cancer than the general population.

Perhaps even more intriguing was the discovery of a link between certain disruptive BAP1 variants and higher levels of IGF-1, a hormone and growth factor associated with cancer growth and brain development. This finding opens up new possibilities for targeted therapies aimed at inhibiting the harmful effects of these variants.

“This research could mean more accurate interpretation of genetic tests, earlier diagnoses and improved outcomes for patients and their families,” adds Professor Clare Turnbull, the clinical lead of the study.

Study Limitations

While this study represents a significant leap forward in our understanding of cancer genetics, it’s important to note that it focuses primarily on a single gene, BAP1. Further research will be needed to apply this technique to other genes associated with cancer and other diseases.

Additionally, while the study’s inclusive approach helps address the historical underrepresentation of non-European populations in genetic research, continued efforts will be necessary to ensure that genetic insights are truly accessible and relevant to all people, regardless of ancestry.

Discussion & Takeaways

For patients and healthcare providers, it offers the potential for more accurate genetic testing, earlier diagnoses, and improved treatment outcomes. For the scientific community, this study demonstrates the power of comprehensive genetic analysis in uncovering new insights into disease mechanisms. The identification of IGF-1 as a potential therapeutic target is particularly exciting, as it could lead to the development of new drugs to slow down or prevent the progression of certain cancers.

“Our aim is to apply this technique to a wider range of genes, potentially covering the entire human genome in the next decade with the Atlas of Variant Effects,” concludes Dr. David Adams, senior author of the study.