BreastDx ClearTM is a multi-gene test that analyzes 16 breast cancer susceptibility genes.
What is hereditary cancer?
Cancer development is a complex process. If certain genes are mutated and do not give cells proper instructions about when to grow and divide, then cancer could develop. Environmental factors, such as UV light, tobacco and diet can increase mutation rates. Some of these mutations will be repaired, but some mutations will not. These mutations will be present in some cells in the body and this will increase the risk of cancer development.
However in families with hereditary forms of cancer, a mutation is present in a very important gene and is present in all cells in the body. Inheriting a cancer-causing mutation in one of the cancer-associated genes does not mean that cancer will definitely occur. It means only that your risk is higher than for someone who does not carry such a mutation in their cells.
Some types of cancer have a significant hereditary component and can develop due to a mutation in one of the hereditary cancer predisposition genes. Most breast cancer occurs by chance however about 10% is inherited. Mutations in certain genes are known to be significantly associated with increased risk of breast and/or ovarian cancers and other types of cancer. About 50% of all hereditary breast cancer cases can be attributed to BRCA1/2 mutations and about 30% of the cases are associated with known mutations in other genes, such as ATM, CDH1, PALB2, PTEN, TP53 and others.
Are you at high risk for breast or ovarian cancer?You could have an inherited risk if:
- You or a family member (mother’s or father’s side) were diagnosed with breast cancer at age 50 or younger
- Breast and ovarian cancer in the same woman in your family
- Male breast cancer at any age
- 3 or more cases of breast cancer on the same side of the family
- 3 or more cases of breast, ovarian and/or pancreatic cancer on the same side of the family
- Ashkenazi (Eastern European) Jewish ethnic background and a personal or family history of Hereditary Breast and Ovarian Cancer Syndrome
What is BreastDx ClearTM?BreastDx ClearTM is an expanded multi-gene test that analyses point mutations, gross deletions and duplications in the following genes associated with inherited breast, ovarian and some other types of cancer: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, FANCC, MRE11A, NBN, PALB2, PTEN, RAD51C, RAD51 D, STK11 and TP53. We use next-generation sequencing (NGS) technology to identify variants in the coding regions of these genes. The identified variants are classified according to the guidelines for sequence variant interpretation of the American College of Medical Genetics and Genomics (ACMG). Variant classification categories include pathogenic, likely pathogenic, variant of unknown significance (VUS), likely benign, and benign with likely benign and benign variants excluded from the report.
- Pathogenic variants - Genetic changes with known clinical significance that is associated with an increased risk of hereditary cancer.
- Likely pathogenic variants – Genetic changes that have some preliminary clinical data indicating an association with hereditary cancer but not sufficient to make a definitive determination of pathogenicity.
- Variants of uncertain significance (VUS) – Genetic changes with either conflicting or no supporting data to determine their pathogenicity.
- Negative Result – No variant of clinical or uncertain significance was detected. Negative result does not eliminate the risk of developing cancer. Benign variants that have sufficient evidence to be considered of no clinical significance and likely benign variants that are not likely to increase the risk of cancer will not be shown on the report.
What are the possible benefits of BreastDx Clear testing?Any hereditary cancer susceptibility testing reduces the uncertainty about the risks of cancer for people and their families. Such testing may be able to explain the cancer history in your family. If a cancer predisposing mutation is identified, it can help your doctor to guide your medical care and decrease the risk of breast and ovarian cancers.
BreastDx ClearTM genesBreastDx ClearTM is a multi-gene test that analyzes 16 breast cancer susceptibility genes. Although all women have some risk of developing breast and/or ovarian cancer at some point in their lives, having a mutation in one of the breast cancer susceptibility genes increases this risk. Men who have a mutation in one of the breast cancer susceptibility genes have an increased risk of breast, prostate, pancreatic, gastric and other cancer types.
|Click on any gene to view its definition|
The BRCA1 protein is involved in repairing damaged DNA. In the nucleus of many types of normal cells, the BRCA1 protein interacts with several other proteins to mend breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, and they also occur when chromosomes exchange genetic material in preparation for cell division. By helping to repair DNA, the BRCA1 protein plays a critical role in maintaining the stability of a cell's genetic information.
Research suggests that the BRCA1 protein also regulates the activity of other genes and plays an essential role in embryonic development. To carry out these functions, the BRCA1 protein interacts with many other proteins, including other tumor suppressors and proteins that regulate cell division.
The BRCA2 protein is involved in repairing damaged DNA. In the nucleus of many types of normal cells, the BRCA2 protein interacts with several other proteins to mend breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, and they also occur when chromosomes exchange genetic material in preparation for cell division. By helping to repair DNA, the BRCA2 protein plays a critical role in maintaining the stability of a cell's genetic information.
Researchers suspect that the BRCA2 protein has additional functions within cells. For example, the protein may help regulate cytokinesis, which is the step in cell division when the fluid surrounding the nucleus (the cytoplasm) divides to form two separate cells. Researchers are investigating the protein's other potential activities.
E-cadherin is one of the best-understood cadherin proteins. In addition to its role in cell adhesion, E-cadherin is involved in transmitting chemical signals within cells, controlling cell maturation and movement, and regulating the activity of certain genes. E-cadherin also acts as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way.
The CHK2 protein is activated when DNA becomes damaged or when DNA strands break. DNA can be damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, and breaks in DNA strands also occur naturally when chromosomes exchange genetic material.
In response to DNA damage, the CHK2 protein interacts with several other proteins, including tumor protein 53 (which is produced from the TP53 gene). These proteins halt cell division and determine whether a cell will repair the damage or self-destruct in a controlled manner (undergo apoptosis). This process keeps cells with mutated or damaged DNA from dividing, which helps prevent the development of tumors.
The FANCC protein is one of a group of proteins known as the FA core complex. The FA core complex is composed of eight FA proteins (including FANCC) and two proteins called Fanconi anemia-associated proteins (FAAPs). This complex activates two proteins, called FANCD2 and FANCI, by attaching a single molecule called ubiquitin to each of them (a process called monoubiquitination). The activation of these two proteins, which attach (bind) together to form the ID protein complex, attract DNA repair proteins to the area of DNA damage so the error can be corrected and DNA replication can continue.
Nibrin interacts with two other proteins, produced from the MRE11A and RAD50 genes, as part of a larger protein complex. Nibrin regulates the activity of this complex by carrying the MRE11A and RAD50 proteins into the cell's nucleus and guiding them to sites of DNA damage. The proteins work together to mend broken strands of DNA. DNA can be damaged by agents such as toxic chemicals or radiation, and breaks in DNA strands also occur naturally when chromosomes exchange genetic material in preparation for cell division. Repairing DNA prevents cells from accumulating genetic damage that may cause them to die or to divide uncontrollably.
The MRE11A/RAD50/NBN complex interacts with the protein produced from the ATM gene, which plays an essential role in recognizing broken strands of DNA and coordinating their repair. The MRE11A/RAD50/NBN complex helps maintain the stability of a cell's genetic information through its roles in repairing damaged DNA and regulating cell division. Because these functions are critical for preventing the formation of cancerous tumors, nibrin is described as a tumor suppressor.
The PTEN enzyme is part of a chemical pathway that signals cells to stop dividing and triggers cells to self-destruct through a process called apoptosis. Evidence suggests that this enzyme also helps control cell movement (migration), the sticking (adhesion) of cells to surrounding tissues, and the formation of new blood vessels (angiogenesis). Additionally, it likely plays a role in maintaining the stability of a cell's genetic information. All of these functions help prevent uncontrolled cell growth that can lead to the formation of tumors.
The p53 protein is located in the nucleus of cells throughout the body, where it attaches (binds) directly to DNA. When the DNA in a cell becomes damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, this protein plays a critical role in determining whether the DNA will be repaired or the damaged cell will self-destruct (undergo apoptosis). If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors.
Because p53 is essential for regulating cell division and preventing tumor formation, it has been nicknamed the "guardian of the genome."