What DNA From 2600 Tumors Is Telling Scientists About Cancer

Pablo Tucker
March 17, 2020

"With the knowledge we have gained about the origins and evolution of tumours, we can develop new tools and therapies to detect cancer earlier, develop more targeted therapies and treat patients more successfully", said Lincoln Stein of the project steering committee, in a statement released by the Ontario Institute for Cancer Research. Previously, oncologists found driver mutations in about two-thirds of patients, says Campbell.

"We may have a type of breast cancer and prostate cancer where the driver mutations are similar", said Joachim Weischenfeldt, a co-author and associate professor at the University of Copenhagen.

Until recently, cancer DNA mutation analyses had been focused on small alterations in "coding regions" of DNA - the roughly 1 per cent of DNA that is responsible for making proteins.

For every cancer there are approximately five genetic scars, or DNA mutations. "We have studied and analyzed the whole genome, and our analyses of mutations that are affecting cancer genes have enabled us to genetically explain 95% of the cancer occurrences we have studied by means of mutations", says coauthor Joachim Weischenfeldt, associate professor at the Biotech Research & Innovation Centre at the University of Copenhagen and the Finsen Laboratory at Rigshospitalet.

In the current study, the researchers applied seven different pathway and network analysis methods to noncoding regions of whole genome sequences from more than 2,500 cancer patients - the largest collection to date of uniformly processed cancer genomes.

This study suggests that since early-stage mutations are generally consistent within a cancer type, they could be targets for the prevention, early detection, and treatment of the disease. Eventually, it will also help scientists understand how cancer forms, and help in the formulation of new treatments and therapies for cancer. Sequencing a cancer genome is still expensive, though the cost is falling, says Campbell.

The global study - carried out by scientists at The Institute of Cancer Research, London, the Mayo Clinic in Rochester, US, and the University of Leeds - is the first to show that APOBEC3B's role in driving cancer evolution can be used to create vaccines that can boost the immune response. A huge new trove of data explores how genetic changes drive tumor growth. Driver genes are genes whose mutations are linked to development of a disease, in this case cancer.

Only about half of all the mutational signatures have known causes, triggers like tobacco smoke or radiation.

Causes of cancer are being catalogued through an worldwide study revealing the genetic fingerprints of DNA-damaging processes that drive cancer development.

However, at this stage, the results can not be used to test for cancers in people. The result is the largest database of reference mutational signatures ever. This study now demonstrates that APOBEC3B could also be used to increase the effectiveness of new treatments that use immunotherapy to attack tumours. From numerous patients, in addition to genome sequence data, the project had collected gene expression data - measuring which genes are active in a patient's tumor. "DNA can be mutated in a variety of ways, from changing single bases to removing entire sections of genetic code", Haradhvala said. "All of these shape and mold the genome during cancer development".

The Pan-Cancer Project brought together over 1,300 researchers globally to tackle the mammoth task of sequencing the genomes of 38 types of cancer in almost 2,800 patients.

Dr Daniel Brewer, from UEA's Norwich Medical School, told The Telegraph: "We do not know whether the cancer has just created an environment that the viruses find attractive or whether the viruses are causing the cancer".

The researchers said: "Our study sheds light on the typical timescale of... tumour development, with initial driver events seemingly occurring up to decades before diagnosis".

The studies are also a major step toward personalized care for every cancer patient, by moving closer to a comprehensive list of cancer-causing mutations that oncologists could one day use to pinpoint the cause of a patient's cancer.

"Ultimately, what we want to do is to use these technologies to identify treatments that are tailored to each individual patient", said Dr Peter Campbell, from the Wellcome Sanger Institute.

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