Signs of cancer can be spotted years before diagnosis, says study that could lead to early detection
The landmark project represents the culmination of more than a decade of work in studying the cancer genome
Early signs of cancer can appear years before the disease is diagnosed in a person, says the largest ever study of cancer genetics.
Developing tests for these genetic signs could provide new ways to spot cancer early, say researchers who analyzed 47 million genetic changes in more than 2,600 human tumors, across 38 cancer types. This ranged from common cancers like colorectal and breast cancers to rare cancer types, including pancreatic and brain cancers.
Cancer occurs when mutations or changes are introduced into healthy cells as they grow and divide. A new method developed by the experts can identify mutations that occurred years, sometimes even decades, before the tumor appeared. This opens a window of opportunity for early cancer detection.
The analysis has enabled researchers to create the first complete atlas of genomes to compare the cancers and find the common mutations between them. This is an atlas of the root causes of all common forms of cancer.
It has been created by an effort known as PCAWG — the Pan Cancer Analysis of Whole Genomes or the Pan-Cancer Project. The project, involving over 1,300 scientists and clinicians from 37 countries, represents the culmination of more than a decade of ground-breaking work in studying the cancer genome, as well as creating a huge resource of primary cancer genomes.
The researchers identified cancer types in which mutations tend to happen particularly early, for example, ovarian cancer and two types of brain tumors — glioblastoma and medulloblastoma. The team also revealed the specific changes that are likely to happen early in each of the more than 30 cancer types.
“We've developed the first timelines of genetic mutations across the spectrum of cancer types. For more than 30 cancers, we now know what specific genetic changes are likely to happen, and when these are likely to take place. Unlocking these patterns means it should now be possible to develop new diagnostic tests that pick up signs of cancer much earlier," says Peter Van Loo, co-lead author and group leader in the Cancer Genomics Laboratory at the Crick, in the analysis.
Previously, researchers had studied only the mutations found in protein-coding regions — which is just 1 percent of the genome. The atlas includes the non-coding regions that makeup 99% of the genome.
The findings have been published in over 20 papers in Nature and its affiliated journals.
The cancer 'drivers'
There are many different ways that your genetic blueprint can be damaged and that damage can ultimately give rise to the development of cancer. For each given cancer type there are particular types of damage.
Researchers found on average, any given tumor has four to five key mutations — changes to the genetic blueprint — that are responsible for driving that disease. Those mutations can vary a great deal for each cancer type. Previously, researchers were aware of one or two drivers, that is, genetic changes that contribute to cancer.
By looking at how many times a single change had been replicated and copied across chromosomes, the researchers were able to determine the order in which they happened and the relative timing between them.
Using this method, they found that just over 20 percent of mutations can be considered early events in a tumor's development, with some of these changes taking place years, even decades, before the cancer is found. Of these early mutations, half fall within the same nine genes, meaning there is a small number of genes that are common drivers of early cancer development.
According to the researchers, this work is helping to answer a long-standing medical difficulty — why two patients with what appears to be the same cancer can have very different outcomes to the same drug treatment.
“We show that the reasons for these different behaviors are written in the DNA. The genome of each patient's cancer is unique, but there are a finite set of recurring patterns, so with large enough studies we can identify all these patterns to optimize diagnosis and treatment," said Dr Peter Campbell, member of the Pan-Cancer Project steering committee and Head of Cancer, Ageing and Somatic Mutation at the Wellcome Sanger Institute, UK.
According to the analysis, one of the most common early changes in many cancers, including ovarian cancer, affects a gene called TP53. In glioblastoma, an extra copy of chromosome 7 is very frequently gained early, while for pancreatic and neuroendocrine cancers, several chromosomes are lost in the initial stages of tumor development, says the analysis.
"What's extraordinary is how some of the genetic changes appear to have occurred many years before diagnosis, long before any other signs that a cancer may develop, and perhaps even in apparently normal tissue," said Clemency Jolly, co-lead author and Ph.D. student in the Cancer Genomics Laboratory at the Crick, in the study findings.
University of Melbourne Professor Sean Grimmond, who holds the Bertalli Chair in Cancer Medicine, said the atlas provides a solid foundation to understand which pathways may be damaged in each cancer type. Researchers are close to cataloging all of the biological pathways involved in cancer and having a fuller picture of their actions in the genome.
The team said now that there is a harmonized dataset, experts can start to learn from their knowledge of one cancer and apply it to another. For example, if there is a mutation in breast cancer that may be vulnerable to a particular therapy, we can answer the question of how frequent is that same mutation occurring in other cancer types.
"This research will help identify what types of genetic tests are needed for each cancer type — filling in potential existing gaps that we did not even know were there. It demonstrates better than ever before how similar damage can cause cancer in different tissues — implications mean that a breast cancer drug, for example, could be effectively used to treat oesophageal cancer,” said Grimmond.