The Pan-Cancer Analysis of Whole Genomes project is one of the most comprehensive investigations of cancer genetics to date. It concentrates on genetic mutations that cause healthy cells to turn malignant. As part of the project, a study was conducted with samples from over 2,500 tumors and 38 cancer types. This work led to the discovery that early signs of cancer can appear years, even decades, before diagnostic detection. Meaning there is a longer-than-expected window of opportunity for detecting cancer. Patients could potentially be tested and, if need be, treated at the earliest stages of the disease.
Clemency Jolly, a co-author of the research based at the Francis Crick Institute in London, said:
“What’s extraordinary is how some of the genetic changes appear to have occurred many years before diagnosis, long before any other signs that cancer may develop, and perhaps even in apparently normal tissue.”
According to Cancer Research UK, around 363,000 new cancer cases are reported in the UK annually. Of those, 165,000 resulted in death. That number could dramatically fall if there were a way to detect cancer before symptoms even appear.
Peter Van Loo, co-lead author, also of the Crick Institute, added:
“Unlocking these patterns means it should now be possible to develop new diagnostic tests that pick up signs of cancer much earlier. There is a window of opportunity.
One could try and identify these [early mutations] and do some kind of very sensitive imaging on patients that were positive. Or even further into the future, one could conceive of methods that really targeted these cells and made them light up in an imaging approach or just kill them in one go. That’s a bit of science fiction at the moment.”
The study found that approximately 50% of the earliest mutations happen in only nine genes. That’s a tiny pool of common genes serving as triggers for cells to deviate from healthy development and become cancer. In the future, it should be possible to pinpoint mutations using genetic tests that spot mutations in free-floating DNA – known as liquid biopsies, which is essentially a blood test. These free-floaters are found in the bloodstream and can signify the presence of tumors elsewhere in the body.
Nearly 2,700 whole genomes of cancer samples were sequenced in this study, and 38 different types of tumor mutations were mapped out. The team used a process called the “carbon-dating method” to reconstruct the sequence in which the genomes of cancer cells began to amass errors and ultimately tote large scrambled or copy segments. These mutations were found to happen “particularly early” in two types of brain tumors – medulloblastoma and glioblastoma – as well as in ovarian cancer. The study has been published in the journal Nature.
Lincoln Stein, from the Ontario Institute for Cancer Research in Canada, who is also a member of the Pan-Cancer project steering committee, said:
“The vast majority of work so far has been on the protein-coding portion of the genome. That’s a mere 1%. It’s like trying to put together a 100,000-piece jigsaw puzzle when you’re missing 99% of the pieces and there’s no puzzle box with a completed picture to guide you.”
This new study contributes to the puzzle that is cancer, some of the first detailed insights into the role of the unknown 99% of our DNA – the so-called “dark matter.” It shines some light on how these less-studied realms contribute to cancer. It identifies genes and, in doing so, increases the chances of detecting cancer-causing mutations from approximately 66% to 95%.
Stein added:
“Prior to that, we would be in the dark about roughly one-third of patients that came into the clinic.”
The seeds of cancer are sown well before symptoms appear, and this study provides evidence of that. However, this discovery will not alter any current cancer screenings because more research has to be done. However, it does present the potential of a future cancer diagnostic being able to spot those at risk far earlier.
