Insights from our genome and epigenome will help prevent, diagnose and treat cancer

In 2020, an estimated 10 million people lost their lives to cancer. This devastating disease is underpinned by changes to our DNA — the instruction manual for all our cells.

It has been 20 years since scientists first unveiled the sequence of the human genome. This momentous achievement was followed by major technological advances that allow us to today read the layers of information of our DNA in enormous detail — from the first changes to DNA that occur as a cell becomes cancerous to the complex microenvironments of advanced tumours.

Now, to accelerate discoveries for cancer patients, we need new ways to bring together the different types of complex data we generate to provide new biological insights into cancer evolution.

For today’s issue of Science, my colleagues Professor Toshikazu Ushijima, Chief, Epigenomics Division, National Cancer Center Research Institute (Japan), Prof Patrick Tan, Executive Director, Genome Institute of Singapore and I were invited to review the cancer insights we can currently obtain from analysing DNA in its full complexity and define the future challenges we need to tackle to yield the next step-changes for patients.

The complexity of our DNA

Many imagine our DNA — our genome — as simply a string of letters. In reality, many layers of information — known as the epigenome — completely change its activity.

Our genome can be compared to the different geographical environments of our planet. Much like mountains, islands and oceans are made up of the same basic elements, our genetic sequence of As, Ts, Gs and Cs, forms the basis of complex structural features within our cells.

These geographical environments are created by our epigenome — additional layers of information, which include chemical markers that attach to our DNA (called DNA methylation) and chemical changes to proteins (histones) that wrap around it, which together orchestrate how DNA is organised in three dimensions inside our cells.

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 therapeutic discoveries for patients.

From cancer formation to metastasis

It was previously thought that genetic changes were sufficient to cause a cancer, but it is becoming clear that both the genome and the epigenome changes together play a significant role in cancer evolution. There is some evidence that, for instance, changes to DNA methylation that occur with ageing may predispose cells to genetic changes that cause cancer.

And take cigarette smoking, where scientists have observed DNA methylation changes in the cells lining the lung well before genetic changes and a lung cancer could be detected. To gain new insights into what drives carcinogenesis, we need to map the precise order of genomic and epigenomic changes.

We are also becoming aware that whilst a cancer can accumulate genetic changes, the epigenome is also ‘reprogrammed’ as the cancer transitions from a primary to a metastasising tumour, and eventually may develop resistance to treatment. Understanding these changes may lead to new therapeutic targets that can more precisely treat advanced cancers.

New insight through advanced technologies

Cancer cells reside in a tumour ecosystem with other diverse cell types, including immune cells, and connective cells, called stromal cells. Today, advanced imaging and single-cell technologies are helping us map these cells, as well as genomic and epigenomic changes, in the three-dimensional context of a tumour, and at unprecedented resolution. At Garvan, our researchers are conducting these studies at our intravital microscopy facilities and the Garvan-Weizmann Centre for Cellular Genomics.

A number of international research consortia, including the Human Tumour Atlas Network and the Cancer Research UK Grand Challenge project have been established to study cancers at the single-cell and spatial level. However, these consortia will have to tackle enormous challenges in data integration. In today’s global research environment, we need globally standardised methods to integrate data from different analysis techniques and laboratories.

By revealing not just associations, but the full integration of DNA and cellular changes that occur during cancer formation and progression, we will understand how cancer can be better diagnosed, treated and prevented.

Big data — opportunities and challenges

The last 20 years has seen us develop the technology to show that our genome and epigenome are far more complex than we appreciated. We’re at a point where new cancer insights will come from solving mathematical problems generated from complex and diverse sequencing and imagining data sets.

Our advanced technologies are allowing us to generate a wealth of data. But the challenge now is data integration — humans simply cannot digest all the information we generate. This challenge will be addressed by artificial intelligence, which is where we will need to incorporate computational expertise, looking at and modelling data in innovative ways.

Another critical future challenge will be to translate basic findings into tangible clinical applications. A precise understanding of the multiple steps that lead to cancer formation inside cells may allow us to improve our screening of cancer risk and early detection of cancer. In the future, studies of genetic and epigenetic signatures may help us remove carcinogenic agents and processes from our environment altogether.

For advanced cancers, integrated DNA analyses may help pinpoint overlooked mechanisms that cancer cells use to metastasise, which may be promising targets for therapy development.

As geneticists and epigeneticists, the challenge of integrating our data to study cancer is not unlike the challenge of modelling climate change. Climate modelling requires a huge amount of data from different sources to be combined and contextualised to make predictions about the planet’s future.

This is the same for genomics and epigenomics — we need to understand how the multiple different layers of DNA information work together to elicit the damaging effects of ‘climate change’ in our cells as they become cancerous.

Professor Susan Clark FAA FAHMS is the Genomics and Epigenetics Research Theme Leader and Head of the Epigenetics Research Lab at the Garvan Institute of Medical Research. She is a Conjoint Professor at St Vincent’s Clinical School, Faculty of Medicine and Health, UNSW Sydney, Fellow of the Australian Academy of Science and Fellow of the Australian Academy of Health and Medical Science.

Note: This article have been indexed to our site. We do not claim legitimacy, ownership or copyright of any of the content above. To see the article at original source Click Here

Related Posts
New species of marine plankton discovered, an overlooked source of nutrients in the oceans thumbnail

New species of marine plankton discovered, an overlooked source of nutrients in the oceans

A team of University of Hawai'i at Manoa researchers in the Department of Oceanography's Center for Microbial Oceanography -- Research and Education (C-MORE), along with collaborators at the University of California Santa Cruz, and the California State University San Marcos, have just published a paper in Nature Communications announcing the discovery of two new and…
Read More
Recommended information from ANA, AR application "ANA Motion" calendar thumbnail

Recommended information from ANA, AR application “ANA Motion” calendar

 全日本空輸(ANA/NH)はAR(拡張現実)アプリ「ANA Motion」をリリースした。第1弾として、今年の同社カレンダー「Welcome Aboard」の画像を使用したサービスを始めた。今後はリアルやオンラインのイベントなどで活用するという。 ANAのARアプリ「ANA Motion」。カレンダーの写真にARカメラをかざすと動画が再生されANAのサイトに移る(同社提供)  アプリを起動してカレンダーの写真にARカメラをかざすと、スマートフォン内で動画が再生され、写真だけでは伝わらなかった地域の魅力を伝える。正面以外に斜めからも見られ、約30秒間の動画と音楽が再生される。動画視聴後はANAのウェブサイトへ遷移し、地域のおすすめ情報などを紹介する。  アプリは2021年12月27日から配信開始。初回リリース時はカレンダーのうち、1-3月の静岡と豪州、愛媛の写真でARサービスを体験でき、4月以降も順次更新していくという。 関連リンクANA Motion全日本空輸 ・ANA、日常生活でポイント貯まる新サービス 「ANAポケット」スタート(21年12月20日) ・ANA、羽田空港に無人店舗「ANA FESTA GO」 セルフレジでマイル付与(21年8月26日)
Read More
Index Of News
Consider making some contribution to keep us going. We are donation based team who works to bring the best content to the readers. Every donation matters.
Donate Now

Subscription Form

Liking our Index Of News so far? Would you like to subscribe to receive news updates daily?