I’m going to go out on a limb and say that cancer sucks. I know all too well. The thing about cancer that is most scary, and also most impressive from a scientific standpoint, is its ability to adapt and mutate, to figure out how to beat chemotherapy and the body’s defenses. Once cancer spreads to another organ, it starts to behave differently, as though it’s an alien that has just given birth inside the body, loosing more lethal entities into the system. Cancer mutates, quickly and, at least it seems, intelligently. And while cancer has largely remained a mystery, we know that cancer is caused by genetic mutations. Now, we know more than ever about what underlies those mutations, thanks to scientists from the UK’s Wellcome Trust Sanger Institute, home of the Cancer Genome Project, which has charted 21 mutations that cause 97% of the most common cancers.
In a nutshell, a cancerous tumor starts when something goes wrong in a cell. Cells acquire mutations over time, and while some causes, such as smoking and exposure to UV light, have already been identified, many remain unknown. Pinpointing the causes of the mutations is key to developing new treatments.
When cells mutate, the process leaves a pattern, or what scientists call a “signature.” By studying over 7,000 genomes of people with common forms of cancer, scientists were able to identify 21 signatures that mutate DNA. For many of them, researchers also pinpointed the biological process that caused the mutation. Interestingly, all of the cancers studied contained at least two signatures, indicating that a number of processes work together as cancer develops. Although some cancer types share mutational signatures, some signatures are unique to a particular cancer. Different cancers also often have not only different mutational processes, but also a different number of those processes — for example, ovarian cancer is caused by two underlying mutational processes, while liver cancer is caused by six.
This sounds like the most complicated logic puzzle ever, but scientists hail this as a major breakthrough the understanding and eventual treatment of cancer. “Through detailed analysis, we can start to use the overwhelming amounts of information buried deep in the DNA of cancers to our advantage in terms of understanding how and why cancers arise. Our map of the events that cause the majority of cancers in humans is an important step to discovering the processes that drive cancer formation,” says researcher Serena Nik-Zainal.
One detail they learned is that, of the 30 most common types of cancer, 25 have age-related mutational signatures. I guess that makes sense, as cancer tends to be much more prevalent among older folks. The difference is understanding the relationship between age and genetic mutation, which can then lead to ways to prevent or fix it. While older age is definitely a factor in cancer development, scientists will continue trying to uncover the signature for neuroblastoma, a nerve cell cancer that affects children.
The team also learned that one group of DNA-mutating enzymes (APOBECs) is connected to more than half of the cancers they studied. Ironically, viral infections cause these enzymes to activate, so it’s possible that the cancer-causing signatures actually result from the enzymes’ protective response. It’s also possible that the activation of these enzymes is linked to the onset of a process called kataegis, which is when a bunch of mutations occur in a small genomic region (this happens in breast cancer). This is yet another mystifying, even seemingly paradoxical detail about cancer, but the more we know, the better off we are. Twelve of the signatures remain unexplained, but, hopefully, not for long.