When the Pan-Cancer project began, the researchers have a simple objective: to fully sequence the genomes of different types of cancer and compare them in order to obtain a detailed map of the cellular mutations and alterations at the origin of the most common cancers. And recently, the international team of oncologists, geneticists, immunologists and biochemists, published a complete set of data on this sequencing. The results are unprecedented and considered a real medical breakthrough. They should make it possible to considerably improve cancer diagnosis and treatment.
The Pan-Cancer project brought together more than 1,300 researchers around the world to tackle the gigantic task of sequencing the genomes of 38 types of cancer in nearly 2,800 patients. Their work has produced a host of new discoveries - the number and location of pilot mutations that cause cells to reproduce uncontrollably, with surprising similarities between cancers found in different types of tissue.
The results have been published in nearly two dozen articles in the journal Nature and represent the largest and most comprehensive study ever done on the genomes of several types of cancer.
"Thanks to the knowledge we have acquired about the origins and evolution of tumors, we can develop new tools and therapies to detect cancer earlier, develop more targeted therapies and treat patients more successfully" says Lincoln Stein , member of the project steering committee.
A wide variety of genomes, mutations and cancer processes
Among the main conclusions of the work is the wide variety of cancer genomes. "The most striking result is how different the genome of a person's cancer is from that of another." The study found thousands of combinations of mutations in individual cancers, as well as more than 80 processes that cause the mutations, some related to age and others inherited or linked to lifestyle factors such as smoking. |
| The study found more than 80 cancer processes. This diagram shows some types of genomic alteration classified according to whether they act as cut / paste or copy / paste. Credits: Yilong Li, et al. 2020 |
Research has shown that the early development of certain cancers can occur decades before diagnosis, sometimes even in childhood. Research has also revealed that patterns of mutations, and where they occur, can help identify about 1 to 5% of cancers that cannot be identified by regular diagnoses. A sequenced genome can even reveal misdiagnosis on a type of cancer.
Most of the work on cancer genome sequencing has focused on around 2%, known as “protein coding genes”. But the Pan-Cancer study sequenced whole genomes, discovering new carcinogenic pilot mutations in the remaining 98%, called “non-coding genes”.
A complete mapping of mutations for better diagnoses and treatments
Researchers have found a huge variation in the number of mutations in a given cancer, from very few in some cancers seen in children up to 100,000 in lung cancer samples. And in about five percent of the cases, no known pilot mutation has been found, which implies that there are mutations that have not yet been identified. |
| The Pan-Cancer project sequenced coding genes as non-coding, targeting the entire genome in search of all the genomic elements targeted by cancer mutations. Credits: ICGC / TCGA Pan-Cancer Analysis of Whole Genomes Consortium, 2020 |
Sequencing helps to map the many types of mutations - from changes in simple DNA letters to much larger genetic code insertions or deletions - that can cause cancer. Study also revealed that cancers in different parts of the body are sometimes much more similar than previously thought.
In practical terms, the results will help identify hard-to-diagnose cancers, allow more targeted treatment based on specific pilot mutations behind a particular cancer, and potentially allow earlier diagnosis of developing tumors.
| Bibliography: Pan-cancer analysis of whole genomes The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium Nature volume 578, pages82–93(2020) https://doi.org/10.1038/s41586-020-1969-6 |
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