Zapatka et al. / Nature genetics 2020
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As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) global project, researchers have once again confirmed that viruses are one of the key drivers of some types of cancer. They described known and new associations of viruses with oncogenic mutations, their signatures in the genome, gene activity profiles, and patient survival. The work was published in the journal. Nature genetics.
The other day, the ambitious PCAWG project was completed, the result of a collaboration of two main platforms for research on cancer genetics (TCGA and ICGC) and an international group of invited scientists. The aim of the project was to compare the main types of cancer in different tissues. To do this, pairs of complete genomes were made for healthy and tumor tissue in 2658 cancer patients, and transcriptomes were sequenced for 1222 of them. Processing such a large amount of new data along with additional research made it possible to streamline the existing knowledge and learn a lot: according to the results of the project, 21 articles were published in leading scientific journals (all articles are in the public domain).
–The number of patients with tumors in different tissues
dcc.icgc.org
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-In particular, a separate group of scientists tested the contribution of viruses to the development of tumors on fresh data. Human papillomaviruses, Epstein-Barr viruses, and hepatitis B and C have long been considered drivers of certain types of cancer. However, most of the work is devoted to individual types of cancer or viruses and it is not always possible to compare their results. In the new work, Peter Lichter and his colleagues conducted a global screening, which allowed to confirm or refute the existing hypotheses, as well as to find out new details of the virus-cancer relationship.
Researchers found virus-infected samples first. To do this, they removed from the sequence data all sequences that were similar to human ones, and then, using three different methods, compared the remaining ones with the genomes of known viruses. Those sequences that were little or too similar to the DNA of viruses used in bioengineering were also excluded, but even after this filtration, traces of viruses were found in 16 percent of all samples.
–The number of patients whose viruses were found in tumor (top) or healthy tissues
Zapatka et al. / Nature genetics
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-The main three of the 24 viruses found – alpha papillomavirus, Epstein viruses – Barr and hepatitis B – are well known for their oncogenicity. They were mainly localized in diseased tissues: papillomavirus in cervical, head and neck cancers (HNSCC), Epstein-Barr virus were found in the stomach and esophagus, and hepatitis B virus in the liver.
Presumably, the mechanisms that trigger the “viral” cancer and the usual one are different, and a new work found confirmation of this. By comparing the number of typical driver mutations (e.g. in a gene P53) the researchers found that in patients with papilloma and hepatitis B viruses they are significantly less than in cancers of the same type without viruses. Apparently, viral oncogenes already affect the cells enough, and for their transformation into cancerous appearance of internal breakdowns is excessive. So, for the hepatitis B virus, it turned out that his DNA loves to integrate into the human genome in the middle of the TERT gene, whose activity determines the ability of the cell to divide. The integration of the virus did not break this gene, but rather strengthened its work.
Another virus, an MMTV potentially associated with breast cancer, was found in only one sample – and it was a sample of renal carcinoma, so the hypothesis was not confirmed.
For the remaining viruses, their association with cancer was not so obvious. So, the herpes virus of the sixth type was found in many patients with cancer of the pancreas, stomach and intestines, but inside one patient it was found 1.5 times more often in healthy tissue than in tumor tissue. The mechanism of the virus in this case is still unclear.
The fact that some viruses can provoke cancer has been known since the beginning of the twentieth century, but the mechanism of their work still raises questions. Often oncogenic viruses behave very quietly and unnoticed, and years can pass between infection and the development of cancer – if it even starts at all. What is known about oncoviruses at the moment and how you can fight them can be found in our material.
Vera Mukhina
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