Cancer's genetic secrets revealed through massive international study
Cancer is a hugely complicated disease, and understanding how it starts and how it can be treated requires an equally enormous effort from scientists. That effort is well underway with the Pan-Cancer Project, an international collaboration dedicated to analyzing thousands of whole cancer genomes. And now, the comprehensive results are being published in 23 separate papers, revealing new details about cancer’s causes and development, and how it can be classified, diagnosed and treated.
Otherwise known as the Pan-Cancer Analysis of Whole Genomes (PCAWG) Project, the collaboration involves over 1,300 scientists from 37 countries. These researchers analyzed over 2,600 whole cancer genomes of 38 different types of tumors, probing deeper than ever into how the disease alters DNA.
One of the most optimistic outlooks from the project is that while the cancer genome is incredibly complex, it’s also finite. That means that it should be technically possible to document every genetic change that cancer can possibly induce. That information can then be used to diagnose which type of tumor a patient has and personalize a treatment plan based on the unique genome of their cancer.
With so much data to pore over, 16 working groups were established to investigate different aspects of cancer hidden in its genome. The results of this coordinated effort have now been published in a series of almost two dozen papers.
A key finding of the Pan-Cancer Project may be the significant light it’s shed on the genetic roots of cancer. Before now, the genetic causes of up to 30 percent of tumors were unknown. But with this project, the scientists found at least one causal mutation – and on average, four or five – in almost every cancer type, leaving just five percent of tumors with unexplained origins.
To reach this milestone, the project dove into the “darker” parts of the cancer genome, far beyond the sections explored by most studies. Previously, focus had been on the genes that code for proteins, but this only accounts for around one percent of the genome. Instead, this project set out to map the remaining 99 percent.
Scientists expected that within this non-coding region of the genome they would find many new mutations that drive the growth of cancer. After all, plenty had been found in the coding section, so statistically even more should be found in the much-bigger non-coding region.
But surprisingly, that wasn’t the case at all. The analysis revealed that only about 13 percent of driver mutations reside in this larger area. That suggests that perhaps non-coding driver mutations play a smaller role in cancer than we thought. But it could also just mean that they’re rare and hard to find – this region is very complex, after all.
In another of the studies, researchers tracked the progression of cancer through genetic changes, including some that precede the tumors appearing. In some cases, the team found that certain genetic changes occurred years or even decades before the patient was diagnosed with cancer. And since these early-stage mutations are fairly consistent for a given type of cancer, they could potentially be used as an early detection method. That would allow doctors to intervene much sooner, preventing the disease from taking hold.
This is just a small fragment of the research presented today from the Pan-Cancer Project, and it gives scientists a lot to chew on. While some teams will continue to probe the unknown depths of cancer genomes, others will explore how the new findings could be developed into clinical applications.
“The findings we have shared with the world today are the culmination of an unparalleled, decade-long collaboration that explored the entire cancer genome,” says Lincoln Stein, a member of the project steering committee. “With the knowledge we have gained about the origins and evolution of tumors, we can develop new tools and therapies to detect cancer earlier, develop more targeted therapies and treat patients more successfully.”
This batch of results from the Pan-Cancer Project were presented in 23 papers, all published in Nature and its affiliated journals.