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Australia is at the forefront of cutting-edge cancer genomics research, with DNA sequencing helping specialists make informed treatment decisions, write Amy McCart Reed, Tiffany Boughtwood and Peter Simpson.
Cancer is a genetic disease.
Changes in specific genes are required to initiate a cancerous growth — be they inherited or acquired later in life.
Scientists use a range of technologies to examine the DNA of both cancerous cells and normal cells and to understand the kinds of genetic changes that have set the cancer on its path.
We can study genetic changes to understand the growth and impact of different cancers.
These same technologies are applied to bacteria and viruses and can help us to understand how they evolve and spread.
As the costs of these kinds of tests plummet, doctors and patients are likely to encounter more and more diagnostic and therapeutic opportunities using genomics.
The study of the DNA sequence and the number of copies of all the genes, their structure and function, is called “genomics”.
DNA sequencing
DNA sequencing is used to determine the order of coding bases in DNA.
This can be done for selected genes relevant to a person’s condition (a “panel”), selected parts of genes (“exome”), or most or all of the person’s DNA (the genome; ie, whole genome sequencing).
If we think of the whole genome as a book, then, in this example, exome sequencing is a chapter of the book, and panel sequencing is a selected few sentences.
DNA sequencing tells us where the errors in the genes are, and we can then infer the consequences of the change.
Sometimes, large regions of the DNA, involving numerous genes, are lost or gained (often in high numbers) during DNA replication, and these changes in DNA copy number are very important in the uncontrolled growth of cancer.
Genomics is revolutionary
Genomics has revolutionised the clinical management of some cancers.
In fact, precision oncology, or the specific tailoring of treatments to individuals, is fast becoming a reality for the management of a number of cancers in Australia.
We can now use DNA changes, or patterns of changes, to predict which drugs might be effective, as well as to decide in which patients to use more aggressive therapy.
We can also use the genomic information to predict which patients may have a toxic response to some drugs.
Same treatments, different organs
Furthermore, it has become clear that some cancers arising in different organs (eg, breast or prostate) can have the same kinds of genomic changes, meaning the same kind of therapy can be equally effective for these patients.
This is important as it means there are existing drugs used for patients with breast cancer, that could also be used for patients with prostate cancer.
When you don’t need much DNA sequencing
Some cancer types have very well characterised genetic changes, so only a small amount of DNA sequencing is required to identify the significant change (variant) that can be targeted with precision oncology.
For example, in melanoma, a specific variant in the BRAF gene can predict response to drugs such as vemurafenib.
This can be done with a panel sequencing test, which is small, fast and cost-effective.
When you need more extensive DNA sequencing
On the other hand, breast cancer encompasses a very diverse group of cancers.
In the past decade, it has become clear that no two breast cancer genomes are the same, and even the most commonly altered genes are only present in about 30% of patients.
This means that evaluating a small number of genes is not particularly useful for breast cancers and that reporting on the whole genome would be more informative.
Whole genome sequencing – closer than you think
Of interest to doctors and patients is that our research shows that whole genome sequencing is informative and achievable in the breast cancer clinic in Australia.
There are internationally accepted guidelines for assessing whether a genetic alteration is a reliable predictor of benefit from different drugs (ESCAT), and these guidelines are applied when analysing the data.
It is important for doctors and patients to be aware that not all genetic alterations are well characterised yet and may not have a matched drug proven to be effective.
Australia at the forefront
Australia has recently seen the culmination of several years of cutting-edge genomics research resulting from significant research investment.
For example, Australian Genomics, which was established as the Australian Genomics Health Alliance with $25 million funding from the National Health and Medical Research Council, the Medical Research Futures Fund (Genomic Health Futures Mission), and state-based programs, including Queensland Genomics, will likely have a similar impact.
In fact, these programs have built critical infrastructure, for example Shariant and information portals with standardised guidelines.
The programs also educated the clinical workforce around the ethics and impact of genomics for cancer care, but also for many other diseases including those of the heart, lung and kidney.
As noted, a relatively modest financial investment has resulted in significant output, pushing us closer to using genomics in standard-of-care across many disciplines.
Dr Amy McCart Reed is a Research Fellow at the Centre for Clinical Research in the University of Queensland’s Faculty of Medicine, with expertise in genomics and molecular pathology, and a passion for clinical research and biobanking.
Tiffany Boughtwood is the Managing Director of Australian Genomics.
Associate Professor Peter Simpson is group leader in Cancer Genomics at the University of Queensland’s Centre for Clinical Research, and a Senior Lecturer in the University of Queensland’s MD Program.
The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.
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