Cancer is a genetic disease, caused by specific changes to the genes controlling the way cells function, particularly how they grow and divide. Genes are functional units of heredity made up of DNA containing instructions to produce proteins, which perform important functions in the body. These instructions are transcribed into RNA ‘messenger’ molecules before the proteins are produced. However, this transcription process can go awry and develop into cancer, which in turn interacts with DNA outside the gene, including DNA coding for endogenous retroviruses. Now, a study from researchers led by the Francis Crick Institute shows ancient DNA holding ‘echoes’ of viruses that once infected our ancestors millions of years ago could help the immune system to identify and kill modern-day cancer cells. The team states they identified viral DNA reactivated by cancer, producing products the immune system can see. The hope is the immune system can then be trained to spot these products to selectively target cancer cells. The opensource study is published in the journal Genome Research.
Previous studies show over millions of years, ancient humans were infected with countless viruses, with sections of their DNA now making up more of a person’s genome than human genes. Approximately 8% of the human genome is made up of retroviral DNA, while known genes only make up 1-2%. This viral DNA typically lies dormant, as it is either non-functional or humans have evolved to suppress it. However, when a cell becomes cancerous, some of these suppression mechanisms can fail and this ancient viral DNA can be reactivated. The current study identifies and records fragments of DNA in the human genome left behind by viruses that infected primordial humans.
The current study utilizes a technology called ‘RNASeq’ to study the effects of endogenous retroviruses on transcription in 768 patient samples from 31 different cancer types. The researchers built a catalog of over 130,000 different RNA transcripts produced by endogenous retroviruses, half of which had not been previously discovered. Results show roughly 6,000 transcripts specifically found in cancer samples were not found in healthy tissue.
The lab states many of these were specific to the type of cancer, with most individual cancers expressing high levels of a few hundred transcripts; therefore, they focused on melanoma-specific transcripts and applied an algorithm to predict which could code for material visible to the immune system. They go on to add they identified nine unique peptides specific to melanoma and produced by ancient DNA visible to the immune system. They conclude their approach could form the basis of future cancer therapies where the immune system is vaccinated to recognize and attack cancer cells presenting these peptides.
The team surmises they have identified and recorded a massive database containing RNA sequencing for non-coding ancient viral DNA involved in cancer. For the future, the researchers state by assembling a comprehensive transcriptome, they have extended knowledge of endogenous retroviruses and their potential involvement in cancer.
Source: The Francis Crick Institute
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