Understanding Genetic Testing in Cancer

by Jason Wasserman MD PhD FRCPC
March 27, 2026

Genetic testing is becoming an increasingly common part of cancer care. However, it exists in two very different forms that are often confused — and this confusion is important because the results can have very different implications. One type of genetic test looks at the DNA of the cancer cells themselves, looking for changes that affect your treatment. The other looks at the DNA in your blood or saliva, looking for inherited changes that were present from birth and that may have raised your risk of developing cancer, and may affect the cancer risk of your biological relatives. Both are valuable. Both are common. But they are not the same test, and a result from one tells you nothing about the other. This article explains the difference, describes what to expect from each type, and helps you understand what a genetic result actually means for you and your family.

Two types of genetic testing: somatic and germline

The word “genetic” means relating to DNA — the molecule that carries the instructions for how your body works. Every cell in your body contains a complete copy of your DNA. But when doctors talk about genetic testing in cancer, they are usually referring to one of two very specific things:

Somatic testing: looking at the tumour’s DNA

A somatic change is a DNA change that arises during a person’s lifetime and occurs only in cancer cells. “Somatic” comes from the Greek word for body — these are changes to a specific group of cells in the body, not changes that were present from conception.

Somatic testing is performed on tumour tissue — the sample collected during a biopsy or during surgery. It looks for mutations, gene rearrangements, protein expression levels, and other molecular changes in cancer cells to guide treatment decisions. Results like KRAS mutations, EGFR mutations, HER2 amplification, and MMR deficiency are all findings from somatic testing.

Somatic changes are not inherited and cannot be passed on to children. They exist only in the cancer cells, not in the rest of the body. A somatic KRAS mutation found in a colorectal cancer tumour does not mean your children are at risk of carrying a KRAS mutation.

Germline testing: looking at your inherited DNA

A germline change is a DNA change that was present in the egg or sperm cell at the moment of conception, and is therefore carried in every cell of the body from birth. “Germline” refers to the germ cells — the cells that pass genetic information to the next generation.

Germline testing is performed on a blood or saliva sample — not on tumour tissue. It looks for inherited mutations passed down from a parent and may be passed on to children. The most well-known examples are mutations in the BRCA1 and BRCA2 genes, which significantly raise the lifetime risk of breast and ovarian cancer, and mutations in the MMR genes (MLH1, MSH2, MSH6, and PMS2) that cause Lynch syndrome.

Germline mutations are hereditary. A confirmed germline mutation means that each biological parent, sibling, and child of the affected person has a 50% chance of carrying the same mutation — and could benefit from their own genetic testing.

The same gene, two very different meanings

It is possible to have a somatic mutation and a germline mutation in the same gene, and these are completely different findings. For example, a BRCA2 mutation found in tumour tissue during somatic testing may be either somatic (arose in the cancer cells only, not hereditary) or germline (inherited, present throughout the body). Only germline testing — a blood or saliva test — can tell which it is. This distinction is critical because a somatic BRCA2 mutation affects treatment planning (specifically, eligibility for PARP inhibitor drugs), while a germline BRCA2 mutation affects hereditary cancer risk for the whole family.

When your pathology report includes the result of a somatic test, it cannot tell you whether the underlying mutation is also germline. If your oncologist or the results suggest a hereditary mutation may be present, a separate germline test will be arranged.

When is germline testing recommended?

Germline genetic testing is recommended when there is a reason to suspect that a cancer may have developed because of an inherited gene mutation. This can be triggered in several ways:

A somatic tumour test suggests a hereditary cause. Some somatic findings strongly point toward a germline mutation—for example, loss of MLH1 and MSH2 proteins on MMR testing in a pattern not explained by a sporadic cause, or a BRCA mutation identified on tumour testing in a person with ovarian cancer. In these situations, germline testing is recommended to confirm or rule out a hereditary origin.
The cancer itself is associated with a hereditary syndrome. Some cancer types — such as ovarian cancer, male breast cancer, and certain early-onset cancers — are strongly enough associated with hereditary syndromes that germline testing is now recommended for all patients regardless of somatic results or family history.
A personal or family history raises suspicion. A strong family history of cancer — particularly cancers diagnosed at young ages, multiple cancers in the same person, or the same type of cancer appearing in several close relatives — may prompt germline testing even when the tumour itself has not triggered it.
A clinical need for hereditary risk information. Knowing whether a cancer is hereditary can affect surgical decisions (for example, whether to remove both breasts or both ovaries), ongoing surveillance plans, and the clinical management of the patient in the future.

What does germline testing involve?

Germline testing is usually a straightforward process. It involves providing a blood or saliva sample, which is then sent to a specialised laboratory. The laboratory analyzes DNA from normal (non-cancer) cells in the sample to look for inherited mutations in specific genes.

Which genes are tested depends on the clinical situation. Some tests look at a single gene or a small panel relevant to a specific hereditary syndrome (for example, BRCA1 and BRCA2 testing for hereditary breast and ovarian cancer). Others use a broader multi-gene panel that simultaneously examines many genes associated with various hereditary cancer conditions. The choice of test is guided by your specific cancer type, personal history, and family history, and is usually recommended by a genetic counsellor or oncologist.

Results typically take two to four weeks. You will usually receive the results in a dedicated appointment — either with a genetic counsellor or with your oncologist — where the findings are explained and their implications discussed in detail.

What do germline results mean?

Germline test results are usually reported in one of three categories:

Pathogenic or likely pathogenic variant. A mutation was found that is known (or very likely) to increase cancer risk. This is the result that carries hereditary implications for the patient and their family. The specific mutation identified, which gene it is in, and what it means for cancer risk will all be explained in detail.
Negative (no mutation detected). No pathogenic mutation was found in the genes tested. This does not guarantee that there is no inherited risk — a negative result means no mutation was found in the genes that were included in the test, not that the person has zero inherited cancer risk. Family history and other clinical factors still matter.
Variant of uncertain significance (VUS). A DNA change was detected, but its significance is not yet known. Scientists have not yet collected enough data to determine whether this particular variant increases cancer risk or is simply a benign variation in the DNA. A VUS is not a positive result and should not be treated as a diagnosis of hereditary risk. As research accumulates, VUS results are periodically reclassified, and your genetic counsellor can monitor this over time.

What is a genetic counsellor, and when should I see one?

A genetic counsellor is a healthcare professional with specialist training in inherited conditions and the emotional and practical implications of genetic testing. They are the experts in this field and are central to the germline testing process.

A genetic counsellor can help you decide whether germline testing is appropriate in your situation, choose the right type of test, understand a result once it comes back, and — perhaps most importantly — think through the implications for your family and what steps to take next. They also help with the often complex emotional aspects of receiving a hereditary result, including how to communicate findings to relatives and how to make decisions about surveillance or risk-reducing interventions.

You should expect to see a genetic counsellor if your tumour testing results suggest a hereditary cause, if your oncologist recommends germline testing, or if you are diagnosed with a cancer type that routinely involves hereditary testing (such as ovarian cancer, early-onset breast cancer, or colorectal cancer with dMMR/MSI-H). You can also ask to be referred to a genetic counsellor if you have concerns about family history, even if your tumour results have not triggered testing.

What does a hereditary result mean for your family?

If germline testing confirms a hereditary mutation, this information extends beyond you to your biological family. Each first-degree relative — a parent, sibling, or child — has a 50% chance of carrying the same mutation. Second-degree relatives (grandparents, aunts, uncles, and half-siblings) have a 25% chance. Testing family members who may carry the mutation is called cascade testing.

Relatives who test positive for a hereditary mutation can then take steps to reduce their cancer risk or catch cancers early. These steps depend on which gene is affected and which cancers it is associated with, but may include more frequent cancer screening (such as regular colonoscopies for Lynch syndrome or annual MRI for BRCA mutation carriers), medications that reduce cancer risk, or preventive surgery in some high-risk situations. These decisions are deeply personal and are made with full medical guidance — a hereditary mutation raises risk but does not mean cancer is inevitable.

Sharing genetic information with family members is something many patients find difficult to navigate. Genetic counsellors are well-practised at helping people think through this process, including how to approach conversations with relatives who may not want to know and what to say to children who are too young to be tested yet.

Common hereditary cancer syndromes

The individual biomarker articles in this section cover the specific hereditary implications of each relevant gene. Here is a brief orientation to the most common hereditary cancer syndromes you may encounter:

Hereditary breast and ovarian cancer (HBOC) syndrome. Caused by mutations in BRCA1 or BRCA2. Raises the lifetime risk of breast cancer, ovarian cancer, and (for BRCA2 carriers) pancreatic cancer, prostate cancer, and melanoma—one of the most common hereditary cancer syndromes.
Lynch syndrome (hereditary non-polyposis colorectal cancer). Caused by mutations in the MMR genes — MLH1, MSH2, MSH6, or PMS2. Raises the risk of colorectal cancer, endometrial cancer, and a range of other cancers, including stomach, ovarian, urinary tract, and small bowel cancer. Affects approximately 1 in 280 people and is often identified through tumour MMR testing.
Hereditary diffuse gastric cancer (HDGC). Caused by mutations in the CDH1 gene. Raises the risk of a specific type of stomach cancer (diffuse gastric cancer) and also raises the risk of lobular breast cancer.
PALB2 mutations. Mutations in the PALB2 gene raise the risk of breast cancer and, to a lesser degree, pancreatic cancer and ovarian cancer. PALB2 is increasingly included in hereditary breast cancer panels.
Polymerase proofreading-associated polyposis (PPAP). A rare syndrome caused by inherited mutations in the POLE or POLD1 genes and associated with multiple colon polyps at a young age and a raised risk of colorectal and endometrial cancer.

This list is not exhaustive — many other hereditary syndromes exist, and the field is rapidly expanding as more genes are identified and studied. The relevant articles in this biomarker section and in the diagnosis guide library provide more detail on the hereditary implications specific to each cancer type.

Practical questions patients often have

Will a genetic test tell me whether I will get cancer?

No — germline testing tells you about risk, not certainty. A positive result means your risk of certain cancers is elevated compared to the general population. It does not mean you will definitely develop cancer, and it does not tell you when. Many people with hereditary mutations live long, healthy lives by following appropriate surveillance programmes.

Does a negative germline result mean I have no hereditary risk?

Not entirely. A negative test means no mutation was found in the genes that were tested — but not all hereditary cancer risk is explained by currently known genes. If you or your family have a pattern of cancer that seems hereditary, a negative result should be discussed with a genetic counsellor rather than taken as complete reassurance.

Could my children be tested?

Genetic testing of children for adult-onset hereditary cancer syndromes is generally deferred until the child is old enough to make their own informed decision, usually adulthood. For syndromes that cause childhood cancer or require surveillance starting in childhood, earlier testing may be appropriate. A genetic counsellor will advise on the right timing for your specific situation.

Does a hereditary result affect insurance or employment?

This concern is common and understandable. The rules vary significantly by country and jurisdiction. In Canada, the Genetic Nondiscrimination Act (2017) prohibits the use of genetic test results by insurance companies and employers. In the United States, similar but more limited protections exist under the Genetic Information Nondiscrimination Act (GINA). Your genetic counsellor will be able to advise on the specific protections that apply in your region.

Questions to ask your doctor or genetic counsellor

Has my tumour been tested for somatic mutations, and are any of those results pointing toward a hereditary cause?
Should I have germline genetic testing based on my cancer type or my family history?
Which genes would be included in a germline test for my situation?
If a hereditary mutation is found, which of my relatives should be offered testing?
What does a result of “variant of uncertain significance” mean, and will it be re-evaluated over time?
What cancer surveillance or risk-reducing options would be recommended if a hereditary mutation is confirmed?
How does genetic testing affect my insurance or employment rights in my country or province?