What is genetic testing?

What is Genetic Testing?

Genetic testing is the process of looking for changes affecting a gene. This could mean:

  • a spelling mistake (called a mutation or pathogenic variant) in the gene itself,
  • a change in the DNA near the gene that affects how the gene works,
  • or even large changes involving chromosomes that carry many genes

When most people talk about genetic testing, they are thinking of germline genetic testing.

Germline genetic testing looks for inherited mistakes. Germ cells are eggs or sperm. If there was a mistake in the egg or sperm that made you, it will be in the DNA of every one of your cells.

DNA is found in the nucleus of a cell. Luckily, white cells have a nucleus so a simple blood test is all that's needed. Saliva or a cheek swab can also be used.

To learn more about the different types of genetic testing and what they can tell us, read on....

Mutation Search and Panel testing

A mutation search is usually the first genetic test done in an individual or a family. Today, rather than searching each gene one by one, testing is usually done via a panel of genes. So... a breast cancer panel, a colon cancer and polyposis panel or a kidney cancer panel may be used depending on the personal and/or family history.

The test checks the genes for "spelling mistakes" which mean the gene can’t do its job properly. Each gene on the panel may be checked more than 100 times!

Genetic testing is usually done first in an affected person (someone who has had a cancer) as they are the ones most likely to carry a mutation.

Management guidelines have been developed to reduce the risk for people with Hereditary Cancer Syndromes. You can read more about genetic mutations and the cancer syndromes they cause in our Genes section.

Finding no mutation (that is, no Class 5 or Class 4 variants) on a mutation search is called an uninformative result. The test hasn't explained that person's cancer or the cancers in the family. The old term was an inconclusive genetic test. It's not used any more as genetic testing now detects 95% to 99.5% of mistakes (and that's pretty conclusive!).

A variant of uncertain clinical significance (also known as a VUS or Class 3 variant) is a DNA change that is not yet fully understood. Here's more about variants of uncertain clinical significance.

What does the genetic test result mean?

There are 3 possible outcomes of a genetic test involving a mutation search:

  • find a mutation (a "positive" result)
  • find no mutations (an "uninformative" result)
  • or find a variant of uncertain clinical significance

Cancer cannot be inherited but cancer risk can. That's why cancers can run together in some families.

If the mutation detected via genetic testing causes more than one type of cancer or tumour, it's referred to as a Hereditary Cancer Syndrome. The cancer risk over a lifetime may be high and the cancers often occur at a younger age.

If you think that describes your family, read more about family history assessment or have a look at our Genes section to read about specific genes and the Hereditary Cancer syndromes they are associated with.

If you inherit a mutation, it's been there your whole life. Knowing about it means you can do something about it.

Predictive Testing

Predictive testing looks for a specific mutation (also known as a pathogenic variant) in a high risk gene. It's a “yes or no” kind of test: either the mutation found in a blood relative is also present in you or it’s not.

The mutation detected is often referred to as a familial mutation, meaning the genetic change found in that particular family.

Medicare funded predictive testing is available for most breast, ovarian and colon cancer risk genes.

When there is no Medicare item number but the mutation is in a high risk gene, testing will usually be offered if you are seen via a public familial cancer clinic.

You can self funded predictive testing when Medicare funded testing isn't available to avoid the often long wait times in public clinics. Predictive testing usually costs $200 to $250.

Founder Mutations

Some groups of people have been isolated by geography, culture or religion. By chance, particular mutations are more common in some of these groups and are called Founder Mutations.

Founder mutation testing is a special type of Predictive testing. An example is the 3 specific mutations found in the BRCA1 and BRCA2 genes in 1:50 people of Ashkenazi Jewish Heritage.

You can read more about founder mutations in our FAQ.

Somatic Testing

Testing a tumour or cancer is called somatic testing. Somatic testing can be done on a biopsy or the resected cancer. In Australia, a tiny piece of the cancer is stored for 7 to 10 years. That means somatic testing can occur many years after a cancer is diagnosed.

Somatic genetic testing can help to:

  • Determine cancer treatment options via biomarker testing
  • Screen for hereditary cancer syndromes (eg via IHC testing or targeted somatic gene testing)
  • Find druggable targets

Biomarker testing

Biomarker testing is usually Medicare funded as it guides treatment decisions. If the marker (a specific mutation in a gene or a gene over-expression) is present the cancer will respond to some treatments and not others. Common examples are:

  • BRAF testing in melanoma
  • KRAS testing in colon cancer
  • EGFR testing in lung cancer
  • HER2 testing in breast cancer

Most of the time, these mutations have occurred only in the cancer itself and would cause very severe problems if they were inherited.

Immunohistochemical (IHC) testing

Most genes make proteins and the proteins then do something. Using a technique called immunohistochemical (IHC) testing, the tumour can be stained to see if the protein made by the gene is present. If it isn't, it could be due to an inherited (germline) mutation.

IHC testing is usually Medicare funded. Not all proteins are easy to stain for. For example, there is no IHC test for the proteins made by the BRCA1 or BRCA2 genes.

IHC testing is strongly recommended for all colon and uterine cancers, some types of kidney cancers and rare types of tumours called pheochromocytomas and paragangliomas, to name a few examples.

IHC It can be done many years after the tumour or cancer occurred. It can even be done if the patient has died (although this would not be Medicare funded). MMR IHC testing of a colon cancer, even many years after it was removed, can detect the possibility of Lynch syndrome. You can read more about Lynch syndrome in our Genes section.

Somatic testing of a deceased relative's tumour can be used to identify families that may have a hereditary risk for cancer.

Searching for Druggable Targets

When cancers metastasise (spread beyond the local lymph nodes) and standard treatments aren't working, the cancer can be screened for "druggable" targets.

This type of somatic testing may screen 300 genes or more and costs $2,500 to $5,000. Patients need to know that even if a target is found the treatment that matches the target may not be funded under the current PBS criteria.

If somatic testing reveals a mutation in the tumour which may have been inherited, germline testing is recommend.

For example, somatic testing is recommended in ovarian cancer, pancreatic cancer and metastatic prostate cancer. If a mutation is detected in BRCA2, say, this is a druggable target. The treatment, called a PARP inhibitor, is PBS funded for use in ovarian cancer but is not yet funded for use in other cancers.

It is likely that the BRCA2 mutation is just a tumour-related mistake. It is also possible that the BRCA2 mutation was inherited. This can be confirmed using a blood test to look for germline (inherited) mutations. See the section on Predictive Genetic testing for more details.

Germline testing is now Medicare funded if a somatic BRCA gene mutation is detected

Targeted Somatic gene testing

Most genetic mistakes in cancers have built up slowly over time. They were not inherited and are not passed on.

Some cancers are more likely to have been caused by an inherited mutation. In these types of cancers, targeted somatic testing may be recommended, even if that person has died. It guides screening recommendations for blood relatives and may even help save their lives.

This is the case in ovarian cancer, where 10 to 20% of cases are caused by an inherited mutation.

As a result, a national, government-funded research study TraceBack has been set up. This study tests the stored ovarian cancer looking for mistakes in genes such as BRCA1 and BRCA2. If no mutation is detected, it is very unlikely the ovarian cancer was caused by a heritable BRCA1 or BRCA2 mutation.

On the other hand, if a mutation is detected in BRCA1 or BRCA2 in the cancer, it's possible the mutation was present in that person all along, even before they were born. If that's the case, then blood relatives may also carry the same high-risk mutation. Knowing about this possibility, family members can have germline genetic testing looking for that specific mistake. If it is present, there's a lot that can be done to reduce cancer risk.

You can read more about TraceBack here. Enrolling in this study is simple and doesn't cost anything.