Scientists complete most comprehensive analysis of whole cancer genomes

  • Scientists complete most comprehensive analysis of whole cancer genomes

Scientists complete most comprehensive analysis of whole cancer genomes

Cells in cancerous growths keep proliferating because of genetic mutations that prevent cells from knowing when to stop duplicating.

Cancer is a disease of the genome caused by mutations in the DNA of a cell during its replication and division. MD Anderson is one of only 50 comprehensive cancer centers designated by the National Cancer Institute (NCI).

The atlas is composed of the entire cancer genomes from more than 2,600 patients suffering from 38 different tumour types. Alternatively, some cancers, including breast, ovarian, and colorectal cancers, have broad periods of chromosomal instability indicating variable timing.

The analysis is published in Nature as part of a wider collection of 22 papers from the Pan-Cancer project. "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. The researchers then modelled how different types of cancer develop over time.

By completing the most comprehensive study of whole cancer genomes to date, an worldwide team of scientists has garnered deeper understanding of cancer, paving the way for more effective treatment, the Wellcome Sanger Institute said on Wednesday. This showed whether important mutations happened early or late in the cancer's development.

Scientists had already analysed cancer genetics for all of the genes that produce proteins, known as the exome or coding regions. Of the mutations, about 100 fell outside the protein-coding areas of the genome.

On top of the genome analysis of cancer, the project also had a system whereby each research group could freely analyze the data available in the database. This is primarily the result of improved methods for analysing the DNA sequence data, compared with the state of the art in 2013.

Dr Ashok Vaid, chairman, Medical and Haemato Oncology at Medanta, the Medicity, said: "It is an exciting development". "It's the vision we all want to get to", Campbell says. The project brought together more than 1,300 researchers across the world to tackle sequencing the genomes of 38 types of cancer in almost 2,800 patients. Their findings could help doctors deliver cancer therapies tailored to a patient's unique cancer genome, and even help predict cancer years in advance.

The fingerprint study identified new mutational signatures that had not been seen before, from single letter "typo" mutations, to slightly larger insertions and deletions of genetic code. Sequencing a cancer genome is still expensive, though the cost is falling, says Campbell.

These changes can occur years, even decades before the cancer occurs and each type of change of mutation has a distinct signature. This uniqueness is a huge advantage when a patient presents with a cancer that has moved or metastasized.

The findings come after UEA scientists pioneered a new way of finding the bacteria and viruses associated with cancer.

This unprecedented level of data crowd-sourcing means researchers, clinicians and industry can now work together, anywhere across the globe. For example, a drug successfully used to treat a breast cancer may be as effective for treating a pancreatic cancer if the two cancers share the same mutation signature. Despite the extensive array of analytical approaches described in these new reports, the researchers were still unable to identify any driver mutations in 5% of the cancers in their study. It might be possible, in future, to pick up such mutations using so-called liquid biopsies - genetic tests that detect mutations in free-floating DNA carried in the blood that can indicate the presence of tumours elsewhere in the body.

"To me, the most striking finding out of all of this...is just how different one person's cancer genome is from another person's", said Peter Campbell, M.D., Ph.D., member of the Pan-Cancer steering committee and head of cancer, aging and somatic mutation at the Wellcome Sanger Institute, during the press conference.