As our cells age or divide, errors can accumulate in the genome they carry, which can lead to cancer, and a variety of environmental and genetic factors can influence the development of cancer in an individual. To learn more about this process, more than 1,300 scientists participated in an international project called the Pan-Cancer Analysis of Whole Genomes (PCAWG), which yielded many new insights into the genetics underlying and driving cancer.
The study used data obtained from over 2,600 tumors that represented 38 different types of cancer, as well as The Cancer Genome Atlas to outline the genetic changes that occur as cancer develops. The researchers created this type of timeline for several kinds of cancer including colorectal and ovarian adenocarcinoma.
"We can map out the point mutations arising throughout normal aging to create a molecular clock for the human genome, akin to tracking the rings of a tree," said Moritz Gerstung, Group Leader at EMBL-EBI. "This provides us with a yardstick to estimate the age of some alterations seen in cancer, and to measure how far a tumor has progressed."
The work suggested that the development of tumors happens over the course of a lifetime, and the mutations that eventually give rise to cancer may occur decades before cancer has progressed to the point of diagnosis.
"We've observed that changes in chromosome count within tumor cells typically occur late during tumor evolution. However, in some cases, such as in glioblastoma multiforme tumors, these changes can occur decades before diagnosis," explained Stefan Dentro, Postdoctoral Fellow at EMBL-EBI. "Typically, cells don't survive for very long with an odd number of chromosomes, but somehow these cells do; possibly founding a tumor that is detected many years later."
"We've developed the first timelines of genetic mutations across the spectrum of cancer types," added Peter Van Loo, group leader in the Cancer Genomics Laboratory at the Francis Crick Institute. "For more than thirty 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."
Cancer cells carry a host of mutations, which can obscure the earliest errors. This chronology of cancer development may help us learn more about the mechanisms underlying the progression of cancer. If a mutation happens early on, it might be useful as a diagnostic tool that can help stop cancer from forming or getting worse.
"To a large extent, cancer development is an unfortunate consequence of the normal aging of our cells," said Gerstung. "Fully understanding the molecular progression of the disease is the first step towards identifying targets for early detection and perhaps treatment. The observation that many genetic alterations were already present years before the cancer was diagnosed provides a window of opportunity to detect aberrant cells before they become fully malignant."