Science Special Issue: New insights into the impact of genome and epigenome on cancer

In 2020, an estimated 10 million people will die from cancer

It has been 20 years since scientists first published the sequence of the human genome

Now, in order to accelerate the discovery of cancer patients, we need new methods to integrate the different types of complex data we generate and provide new biological insights into cancer evolution

In today's "Science" magazine, Professor Clark, Professor Toshikazu Ushijima, and Professor Patrick Tan reviewed the cancer insights currently available from the analysis of complex DNA and defined future challenges that need to be addressed

The complexity of our DNA

Many people think of our DNA—our genome—as a string of letters

Our genome can be compared with different geographic environments on the earth

These geographic environments are created by our epigenome—an extra layer of information, including chemical markers attached to our DNA (called DNA methylation) and chemical changes in the proteins (histones) that wrap the DNA.

Both our genome and epigenome evolve during the cancer life cycle, and we need to understand these complex changes to improve cancer risk assessment and accelerate the discovery of treatments for patients

From cancer formation to metastasis

In the past, it was thought that genetic changes were enough to cause cancer, but it is now increasingly clear that changes in the genome and epigenome together play an important role in the evolution of cancer

Taking smoking as an example, scientists have already observed changes in DNA methylation in lung cells before genetic changes and lung cancer were detected

We have also gradually realized that although cancer can accumulate genetic changes, the epigenome will also "reprogram" as the cancer metastasizes from the primary tumor to the metastatic tumor, and may eventually become resistant to treatment

Advanced technology brings new insights

Cancer cells and other different types of cells (including immune cells and connective tissue cells called stromal cells) live together in the tumor ecosystem

Many international research consortia, including the Human Tumor Atlas Network and the British Cancer Research Grand Challenge Project have been established to study cancer at the single-cell and spatial level

By revealing not only the association, but the complete integration of DNA and cell changes that occur during the formation and development of cancer, we will understand how to better diagnose, treat and prevent cancer

Big data-opportunities and challenges

In the past 20 years, we have developed a technique to prove that our genome and epigenome are far more complex than we thought
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We are at a moment when new cancer insights will come from solving mathematical problems generated by complex and diverse sequencing and imagination data sets
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Our advanced technology allows us to generate large amounts of data
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But the challenge now is data integration-humans simply cannot digest all the information we generate
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This challenge will be solved by artificial intelligence, which is where we need to combine computing expertise to view and model data in innovative ways
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Another key future challenge will be to translate basic discoveries into actual clinical applications
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A precise understanding of the multiple steps leading to the formation of intracellular cancers may allow us to improve cancer risk screening and early detection of cancer
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In the future, research on genetic and epigenetic characteristics may help us completely remove carcinogens and processes from our environment
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For advanced cancers, integrated DNA analysis may help to identify the neglected mechanism of cancer cell metastasis, which may be a promising target for therapeutic development
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As geneticists and epigenetics, the challenge of integrating our data to study cancer is no different from the challenge of simulating climate change
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Climate models require a large amount of data from different sources for combination and background analysis to predict the future of the earth
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The same is true for genomics and epigenomics-we need to understand how different levels of DNA information work together when our cells become cancerous, thereby triggering the destructive effects of "climate change"
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