Acquired mutations. These are the most common cause of cancer. They occur from damage to genes in a particular cell during a person’s life. This mutated cell, goes on to divide many times and form a tumour. A tumour is an abnormal mass. Cancer that occurs because of acquired mutations is called sporadic cancer. Acquired mutations are not found in every cell in the body and they are not passed from parent to child. Factors that cause these mutations include:
- Ultraviolet (UV) radiation
Biomarker is a biological molecular marker found in body fluids or tissues that is a sign of a normal or abnormal process, or disease. A biomarker is used to see how well the body responds to a treatment for a disease.
BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) are genes that produce proteins to repair damaged DNA. Everyone has two copies of each of these genes—one copy inherited from each parent. BRCA1 and BRCA2 are sometimes called tumour suppressors because when they have certain changes, called harmful or pathogenic mutations, cancer can develop. People who inherit harmful mutations in one of these genes have increased risks of several cancers—most notably breast and ovarian cancer. People who inherited a BRCA1 and BRCA2 mutation tend to develop cancer at younger ages. Each child of a parent who carries any mutation in one of these genes has a 50% chance (or 1 in 2 chance) of inheriting the mutation. Cells that don’t have any functioning BRCA1 or BRCA2 proteins can grow out of control and become cancer.
Break apart translocation is where one end of the gene is labelled red and the other end of the gene is labelled green. Normal copies of the gene are seen as a red-green fused signal (cell on the right). If there is a translocation or rearrangement, the gene breaks into separate red and green signals.
Chromosome. DNA is packaged into small units called chromosomes. A chromosome contains a single, long piece of DNA with many different genes. Every human cell contains 23 pairs of chromosomes.
Clinical cancer trials A cancer clinical trial is a way of testing new approaches in cancer patients. Standard treatment is accepted and well used to treat particular types of cancer. With clinical trials, a new drug is tested against the standard treatment. Patients consider clinical trials to help find a more effective treatment for preventing cancer recurrence or cancer treatment. In a clinical trial every test, procedure, dose of drug is provided according to good clinical practice. Patients talk to their doctor about clinical trials in the treatment decision-making process.
CNV (Copy Number Variation). Is a structural variation where one individual has a different number of copies of a specific gene compared to another individual. The number of variants/repeats can vary between individuals’ genomes. Some people may have two, three or four times the copies in a specific chromosomal region. CNV includes insertions, deletions, and duplications of segments of DNA.
Companion diagnostic testing is a test used to help match a patient to a specific drug or therapy. A companion diagnostic test may identify whether a patient’s tumour has a specific gene change or biomarker that is targeted by the drug. This helps determine if the patient should receive the drug or not.
Dominant diseases can be caused by only one copy of a gene with a DNA mutation. If one parent has a disease, each child has a 50% chance of inheriting the mutated gene.
DNA (Deoxyribonucleic acid) contains the genetic instructions in all living things. DNA is made up of two strands that form a double helix. A DNA strand has four different bases arranged in different orders. These bases are T (thymine), A (adenine), C (cytosine), and G (guanine). DNA is “read” by the order of the bases, Ts, Cs, Gs, and As. The specific order, or sequence, of these bases determines the exact information carried in each gene (e.g., instructions for making a specific protein).
DNA Methylation is a chemical addition to a piece of DNA that turns it on or off.
DNA Mutation is a change in a DNA sequence. DNA mutations in a gene can change what protein is made.
DNA repair genes fix mistakes made when DNA is copied. Many of them function as tumour suppressor genes. BRCA1, BRCA2, and p53 are all DNA repair genes.
If a person has an error in a DNA repair gene, mistakes remain uncorrected. Then, the mistakes become mutations. These mutations may eventually lead to cancer, particularly mutations in tumour suppressor genes or oncogenes.
Environmental Factors can include exposures related to where we live as well as behaviours such as smoking, exercise and lifestyle factors such as foods that we eat.
Epigenetics is the study of changes in phenotype caused by something other than changes in the underlying DNA sequence (for example, DNA methylation).
Familial cancer refers to cancer that appears to occur more frequently in families than is expected from chance alone. While no specific mutation has been linked to these cancers, familial cancer may have a hereditary component that has not yet been identified.
FISH Fluorescence in situ hybridization is a technique used to detect chromosomal abnormalities. FISH is based on DNA probes pairing specific target sequences of sample DNA. Attached to the probes are fluorescent reporter molecules which under fluorescent microscopy confirm the presence or absence of a genetic mutation. It is an established tool in diagnostic and discovery of cancer.
Gene expression is the process where the information stored in DNA is used to convert the set of instructions into a functional product e.g. a protein. Changes in gene expression can affect how much of a protein is made, as well as when the protein is made.
Genes are the body’s instructions and determine how the body develops and is maintained. Some genes prevent cancer developing: if there is a mutation (change) in one of these cancer genes, then the gene does not work correctly and causes an increased risk of cancer. Mutations in several hundred genes can cause an increased risk to specific types of cancer.
Genetic cancer risk 5-10% of all cancer is due to a genetic fault (mutation) which can be inherited. Families with an inherited mutation can benefit from cancer risk screening. Families with an increased risk of cancer often show one of the following clues:
- Several relatives with the same or linked types of cancer
- Relatives diagnosed at particularly young ages (before 50)
- Several affected generations
- Individuals who have been diagnosed with multiple cancers
Cancers which can be linked in some families are Breast, ovarian, prostate, pancreatic, Bowel, womb and stomach cancers
Genetic Counsellor can help explain the risks and benefits of a genetic test, the potential results of a genetic test, what the results mean, how family members may be effected, and direct individuals to relevant patient support groups.
Genetic testing looks at the DNA code for a specific gene or genes known to be associated with cancer. It provides information about the gene(s) which are analysed.
- Normal: means no disease-causing mutation is found
- Positive: a known cancer-causing mutation is found to aid targeted treatment choices and relatives can have testing for this mutation
- Inconclusive: a mutation of unknown significance is found where the lab has found a change in the gene that they cannot interpret
Genetic risk testing helps estimate your chance of developing cancer in your lifetime. It searches for specific changes in your genes, chromosomes, or proteins. These changes are called mutations. Genetic tests include:
- Breast cancer
- Ovarian cancer
- Colon cancer
- Prostate cancer
- Pancreatic cancer
- Kidney cancer
- Stomach cancer
Genetic testing can help:
- Predict your risk of a particular disease
- Find if you have genes that may pass increased cancer risk to your children
- Provide information to guide your therapeutic treatment
- Results can help with management of a condition e.g. precision medicine, increased surveillance screening, or lifestyle changes.
Genetic testing cannot say if you will develop cancer but can tell you if you have a higher risk than most people.
Genomics refers to the study of all of the genetic material in an organism.
Genotype. The genotype of a person is her or his genetic makeup. It can also refer to the alleles that a person has for a specific gene.
Germline mutations can be passed on from parent to child, while mutations that occur in body cells (somatic mutations) cannot be inherited. Germline mutations in BRCA1 or BRCA2 genes increase a woman’s risk of developing hereditary breast or ovarian cancers and a man’s risk of developing hereditary prostate or breast cancers. They also increase the risk of pancreatic cancer and melanoma in women and men. The most commonly mutated gene in people with cancer is p53 or TP53. More than 50% of cancers involve a missing or damaged p53 gene. Most p53 gene mutations are acquired. Germline p53 mutations are rare, but patients who carry them are at a higher risk of developing many different types of cancer.
Hereditary cancer is caused by an inherited genetic mutation. 10-15% of most cancers are due to inherited genetic mutations. It is typical to see a recurring pattern of cancer across two to three generations—like multiple individuals diagnosed with the same type of cancer(s) and individuals diagnosed with cancer much younger than average.
H&E staining to identify and provide important data on cell structure to aid cancer diagnosis.
IHC Immunohistochemistry provides valuable information on expression of proteins within tissues at a cellular and subcellular level.
Immunotherapy is a type of cancer treatment designed to boost the body’s natural defences to fight the cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function.
Methylation plays a vital role in optimising the function of many processes within the body including; DNA repair, Hormone regulation, Immune system health. Energy production, Strengthening the nervous system, Wellness and Protecting against cancer.
Mutations All cancers begin when one or more genes in a cell mutate. A mutation is a change. It creates an abnormal protein. Or it may prevent a protein’s formation. Mutations happen often and may be beneficial, harmful, or neutral. Typically, the body corrects most mutations. A single mutation will likely not cause cancer. Usually, cancer occurs from multiple mutations over a lifetime. That is why cancer occurs more often in older people.
Oncogenes turn a healthy cell into a cancerous cell. Mutations in these genes are not known to be inherited. Common oncogenes are:
- HER2, a specialized protein that controls cancer growth and spread. It is found in some cancer cells. For example, breast and ovarian cancer cells.
- The RAS family of genes, which makes proteins involved in cell communication pathways, cell growth, and cell death.
Oncology is the study of cancer. An Oncologist is a doctor who treats cancer and provides medical care for a person diagnosed with cancer.
PCR assay involves several critical steps, such as DNA extraction from samples, PCR amplification, and detection. It is a highly sensitive and specific method for the amplification and detection of deoxyribonucleic acid (DNA). It is the most widely used technique in molecular biology and can detect as little as a single fragment of DNA. When specific clinical samples are tested by PCR, each procedure is carefully designed. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) enables reliable detection and measurement during each cycle of the PCR process.
PCR Test is a polymerase chain reaction test to detect genetic material such as a virus. The test detects the presence of a virus and if you have the virus at the time of the test. The test can also detect fragments of the virus even after you are no longer infected.
PD-1. A protein found on T cells (a type of immune cell) that helps keep the body’s immune responses in check. When PD-1 is bound to another protein called PD-L1, it helps keep T cells from killing other cells, including cancer cells. Some anticancer drugs, called immune checkpoint inhibitors, are used to block PD-1. When this protein is blocked, the “brakes” on the immune system are released and the ability of T cells to kill cancer cells is increased.
Phenotype is how a person looks (on the outside and inside the body) due to his or her genes and the environment. Phenotype can refer to how a person’s body functions, e.g., whether he or she has a certain disease.
Pre-symptomatic testing looks at several genes to determine if a healthy individual has an increased risk of developing cancer. There are three possible results:
- Normal: there may still be an increased risk of cancer depending on your family history and increased surveillance be recommended by your doctor.
- Positive: a known cancer-causing mutation is found. Cancer surveillance can be targeted, and relatives can have testing for this mutation.
- Inconclusive: a mutation of unknown significance is found.
Prostate is a gland the size and shape of a walnut which grows bigger as you get older. It sits underneath the bladder and surrounds the urethra, which is the tube that carries urine out of the body. The prostate’s main job is to help make semen.
Prostate cancer is common in men across the UK. 1 in 3 men will get prostate cancer in their lifetime. Men with prostate cancer often have no symptoms unless the disease is detected at a late stage. Early personalised profiling of prostate cancer risk can aid surveillance and mange future disease development.
Prostate cancer mainly affects men 40+ and African-Caribbean males are more likely to get prostate cancer.
Protein is made up of building blocks called amino acids. The main role of DNA is to act as the instructions for making proteins. It is actually proteins that make up most of the structures in our bodies and perform most of life’s functions. Proteins are made in cells and are the major parts of cells, which are the vital working units of all living things.
Recessive diseases are where both copies of a gene must have the DNA mutation for a person to have one of these diseases. If both parents have one copy of the mutated gene, each child has a 25% chance of having the disease, even though neither parent has it. In such cases, each parent is called a carrier of the disease. They can pass the disease on to their children, but do not have the disease themselves.
SNPs (Single Nucleotide Polymorphisms) are the most common occurring genetic variation within an individual’s DNA. Each SNP represents a difference in a single nucleotide (DNA building block). These variations in DNA, that occur between genes, act as biological markers to identify genes associated with different diseases.
Sporadic cancer refers to cancer that occurs due to spontaneous mutations that accumulate over a person’s life. Sporadic cancer cannot be explained by a single cause. There are several factors, such as aging, lifestyle, or environmental exposure, that may contribute to the development of sporadic cancer.
Targeted therapy is Treatment that targets specific genes, proteins, or other molecules that contribute to cancer growth and survival.
TMA Trimethylamine production is associated with hardening of the arteries and severe cardiovascular disease.
TMB Tumour Mutational Burden. The total number of mutations (changes) found in the DNA of cancer cells. Knowing the TMB can help plan the best treatment choices. Tumours that have a high number of mutations may be more likely to respond to certain types of immunotherapy.
Tumour suppressor genes are protective genes which normally limit cell growth by:
- Monitoring how quickly cells divide into new cells
- Repairing mismatched DNA
- Controlling when a cell dies
When a tumour suppressor gene mutates, cells grow uncontrollably and may eventually form a tumour. Examples of tumour suppressor genes include BRCA1, BRCA2, and p53 or TP53.
Variant of Uncertain Significance (VUS) is a genetic change whose impact on an individual’s cancer risk is not yet known. Everyone’s genes are slightly different. Some genetic changes (variants/mutations) do not affect the gene’s function and therefore do not increase cancer risk. With genetic testing you might not get a “Normal” or “Positive.” You might get an Inconclusive mutation VUS. Unlike harmful mutations that cause cancer or benign ones that don’t, researchers don’t yet have enough information about VUS to know whether they’re involved in cancer. Almost 20% of genetic tests identify a VUS.
Genetic categories of variants/mutations are ranked from most to least severe.
- Pathogenic (harmful, increased risk of disease)
- Likely pathogenic
- Variant of Uncertain Significance (VUS)
- Likely benign
- Benign (harmless)
The categories follow American College of Medical Genetics and Genomics (ACMG) guidelines and genetic results should be shared with a healthcare professional and discussed with a medical doctor.
Whole genome sequencing (WGS) is used in research, clinical diagnosis and for public health to decode genes and enable characterization to learn more about health for targeted treatment, molecular epidemiology, and viral identification. Whole-genome sequencing data can identify genetic markers of increased or decreased risk of cancer, as well as markers that help define disease subtype. Each person has a unique DNA sequence which is composed of bases (A, T, C, and G). If you know the sequence of the bases, you have identified their unique DNA fingerprint. Determining the order of bases is called sequencing. Whole genome sequencing is a laboratory procedure that determines the order of bases in the genome of person in one process.