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" that 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 on how to reduce cancer risk have been developed 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

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

Hereditary Cancer syndromes occur due to inherited mistakes in key genes. 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 mutations and the Hereditary Cancer syndromes they cause.

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 gene. It's a “yes or no” kind of test: either that mutation is 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 cancer risk is high, testing will usually be offered if you are seen via a public familial cancer clinic. The national eviQ guidelines set out which genes publicly-funded testing should be available for.

You can self-fund 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 (if germline (blood) testing is not possible)
  • 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 may respond to some treatments but may not respond to 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 for rare types of tumours called pheochromocytomas and paragangliomas.

If it wasn't done at the time of diagnosis, IHC testing can even be done many years after the tumour or cancer occurred This is because a small piece of the cancer, called a tumour block, must be stored for 7 to 10 years. Testing can even be done if the patient has died (although this would not be Medicare funded).

For example, MMR IHC testing of a colon cancer is Medicare funded, even many years after the cancer was removed. This testing can detect the possibility of Lynch syndrome, a hereditary cancer syndrome associated with a very high risk of bowel and uterine cancers. 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

A cancer can be screened for "druggable" targets. Testing may include testing for biomarkers, IHC testing or even molecular or genomic testing. This may occur more than once and at different times in the cancer treatment, depending on the goal. For example, chemotherapy and other targeted treatments may be used:

  • Before surgery to reduce the size of a cancer or even kill all the cancer cells (neoadjuvant therapy).
  • After surgery to destroy any remaining cancer cells (adjuvant therapy).
  • To treat advanced cancer after initial treatments, if the cancer has recurred, or for cancers that haven’t responded to treatment so far (second line therapy or palliative therapy).
  • As long term treatment to prevent the cancer coming back or continuing to grow (maintenance treatment).

Testing a cancer for a genetic mutation that is helping the cancer grow (a "driver" mutation) is also called genomic testing, genomic profiling or exome sequencing.

Commonly used cancer panels screen 300 genes or more and cost $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.

Somatic testing can't determine whether the changes are acquired gene changes, unique to the cancer cells, or inherited changes. If somatic testing reveals a mutation in the tumour which may have been inherited, germline testing to sort this out is strongly recommend. See the section on Predictive Genetic testing for more details.

For example, somatic testing is recommended in ovarian cancer, pancreatic cancer and metastatic prostate cancer to guide treatment. If a mutation is detected in BRCA2, for example, this is a druggable target. The treatment, called a PARP inhibitor, is PBS funded for use in ovarian cancer and may be available via compassionate access or via research trials for other cancer types. In this case, germline testing would also be recommended, to see if the BRCA2 mutation was inherited.

Germline (blood) testing is now Medicare funded if a BRCA gene mutation is detected on somatic (tumour) testing.

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.

The stored tumour block from the ovarian cancer can be tested 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.

Of all the BRCA gene mutations detected in an ovarian cancer, 60% just occurred in those cells but 40% were inherited. This is very important information for families!