Last Updated: 04/20/2020

Next Generation Sequencing for Inherited Cancer

Scion Genomics, offers physician ordered hereditary cancer risk assessment testing. Using Next Generation Sequencing we evaluate multiple known cancer genes to target 8 types of hereditary cancers.

Hereditary Cancer Genetic Testing

Hereditary cancer genetic testing looks for mutations in specific genes that are currently known to increase the risk for cancer and may be passed down, or inherited, in a family.

Hereditary Cancer Syndromes

Hereditary cancer syndromes are inherited within a family and result in a higher than normal chance of developing specific types of cancer. The chance is increased that you have a hereditary cancer syndrome in your family when several close relatives have the same type of cancer, develop cancer at an early age, or a family member has more than one type of cancer. Examples of well characterized hereditary cancer syndromes include:

  • Breast and ovarian cancer syndrome
  • Li-Fraumeni syndrome
  • Cowden Syndrome
  • Lynch syndrome

The Power Of Information

If you are found to have a positive test result, it means your risk is increased to develop cancer in the future. Your health care provider can guide you with the steps that can both lower your risk and find cancer earlier through preventive care and screening. Sharing this information with your family members, like your children and siblings, will help them make decisions about testing and their own health care. You can work with your healthcare provider to create a personalized screening and prevention plan, designed to help reduce your risk of developing cancer. This might include earlier and more frequent screenings.

The Power Of Information
What We Offer

What We Offer

  • A free personal and family history assessment to determine whether or not you are at increased risk for an inherited cancer mutation in your family.
  • Testing that can be done from the comfort of your home.
  • Free genetic counseling if you are found to have a mutation in a cancer causing gene or a variant of uncertain significance.

35 Gene Panel and Associated Cancers*

Gene
(Chromosome location)
Breast Colorectal Melanoma Ovarian Pancreatic Prostate Stomach Uterine
APC
(5q22.2)

Familial adenomatous polyposis (FAP) is a colon cancer predisposition condition due to mutations in the APC gene. Individuals with FAP will have multiple pre-cancerous polyps in their colon by, on average, their teens. Over 90% of individuals with FAP develop colon cancer by their mid 30’s. There is also a milder form (attenuated FAP or AFAP) in which individuals will have fewer polyps, and at an older age, than in FAP.

Having a mutation in APC results in an increased risk to develop multiple polyps in the stomach and intestines, and an increased risk for cancers of the colon, stomach, thyroid, pancreas, liver, and central nervous system, as well as others.

There may also be other signs and symptoms in a person having a mutation in the APC gene, like pigmentary changes in the retina of the eye, dental anomalies (e.g. extra or missing teeth), and skin differences (e.g. lipomas).

People with mutations or changes in the APC gene usually have family members with FAP or AFAP.

ATM
(11q22.3)

Females who have a single mutation or change in the ATM gene have an increased chance to develop breast cancer. The increased chance is variable and may depend on the specific mutation a person has. Some mutations may increase the risk to about 65%. There is also increased risk for pancreatic cancer (both genders) and prostate cancer (males), but the risk is not well defined for these.

Ataxia telangiectasia (AT) is a rare progressive genetic condition. People with AT develop an early onset ataxia. They have immunodeficiency and frequent infections. It can cause dilated blood vessels in the eyes and under the skin (telangiectasia). A portion of individuals who have AT will develop cancers such as acute lymphocytic leukemia and lymphoma.

AXIN2
(17q24.1)

Mutations in the AXIN2 have been associated with a potentially increased risk for colorectal cancer. Mutations in this gene are associated with polyposis and oligodontia-colorectal cancer syndrome.

BAP1
(3p21.10)

Mutations in the BAP1 gene increase the risk for a variety of cancerous and noncancerous tumors. People with BAP1 mutations have an increased risk for eye and skin melanoma, mesothelioma, renal cell carcinoma and various other malignancies. In BAP1 tumor predisposition syndrome, cancers tend to occur at a younger age and can be more aggressive than the same cancers in the general population.

BARD1
(2q35)

BARD1 mutations are associated with an increased risk for breast and ovarian cancer. The data is less strong for this gene, so there are unknown risks to other types of cancer.

BLM
(15q26.1)

A single mutation in the BLM gene has a possible increased risk for colon and breast cancer.

If both members of a couple have BLM mutations they are at an increased risk (25%) to have a child with Bloom syndrome. Bloom syndrome is a rare condition that can cause variation in skin pigmentation, sensitivity to the sun, and an increased risk of certain cancers.

BMPR1A
(10q23.2)

Individuals with a mutation in the BMPR1A gene have juvenile polyposis syndrome (JPS). JPS causes multiple non-cancerous polyps or growths to develop in the intestines prior to the age of 20. Individuals with JPS have a 10 to 50 percent risk of developing a cancer of the gastrointestinal tract, the most common being colon cancer.

BRCA1
(17q21)

Mutations in BRCA1 and BRCA2 are the most common causes of hereditary breast and ovarian cancer, a mutation in one of these genes leads to a pronounced increase in the risk of developing cancer. In particular, it leads to an increased risk for female and male breast cancer, ovarian cancer, and to other cancers such as prostate cancer, pancreatic cancer, and melanoma. The risk for each of these cancers varies slightly depending on if the mutation is in BRCA1 or BRCA2. There are well-established published management guidelines if someone has a mutation in one of these genes.

BRCA2
(13q13.1)

Mutations in BRCA1 and BRCA2 are the most common causes of hereditary breast and ovarian cancer, a mutation in one of these genes leads to a pronounced increase in the risk of developing cancer. In particular, it leads to an increased risk for female and male breast cancer, ovarian cancer, and to other cancers such as prostate cancer, pancreatic cancer, and melanoma. The risk for each of these cancers varies slightly depending on if the mutation is in BRCA1 or BRCA2. There are well-established published management guidelines if someone has a mutation in one of these genes.

BRIP1
(17q23.2)

Females with a mutation in the BRIP1 gene have an increased risk to develop ovarian cancer. Risk estimates for male cancers in BRIP1 mutation carriers are currently not available.

Fanconi anemia (FA) is a rare condition that can cause bone marrow failure, skeletal abnormalities, and an increased risk of certain childhood cancers. It is an autosomal recessive condition; therefore individuals with two copies of a BRIP1 mutation, one from each parent, can be affected with FA. There are many other genes that also cause FA.

CDH1
(16q22.1)

Males and females with a mutation in the CDH1 gene have an increased risk to develop stomach cancer characterized as diffuse gastric. Women are also at increased risk for lobular breast cancer.

CDK4
(12q14.1)

Individuals who have mutations in the CDK4 gene have an increased risk to develop non-cancerous atypical moles/nevi and malignant skin melanoma. There have been reports of other types of cancer as well (e.g. female cancers, pancreatic cancer) in individuals with a CDK4 mutation, however, the clinical validity of this data is limited.

CDKN2A
(9p21.3)

Individuals who have a mutation in the CDKN2A gene are at increased risk to develop multiple benign moles, cancers of the head and neck (squamous cell carcinoma) and moist lining of the mouth, nose, and throat, pancreatic cancer, and malignant skin melanoma. This is called Melanoma-Pancreatic Cancer Syndrome, which used to be called Familial Atypical Multiple Mole Melanoma syndrome.

CHEK2
(22q12.1)

Mutations in the CHEK2 gene have been associated with an increased risk for breast and ovarian cancer in females and breast cancer in males. Individuals with a CHEK2 mutation are also at increased risk for colorectal cancer and possibly lung, prostate, thyroid, and kidney cancer. CHEK2 mutations may increase the risk for Li-Fraumeni syndrome which is associated with breast cancer, bone cancer, soft tissue sarcomas and other cancers.

EPCAM
(2p21)

Deletions of the EPCAM gene are the cause of a small portion of Lynch syndrome, or hereditary non-polyposis colorectal cancers (HNPCC). This diagnosis holds an increased risk to a variety of cancer types including cancers of the colorectal tract, stomach, small bowel, hepatobiliary tract, urinary tract, brain, skin, and in females ovarian and endometrium.

GREM1
(15q13.3)

Individuals with a mutation in or affecting the GREM1 gene may be at increased risk for Hereditary Mixed Polyposis syndrome (HMPS). There have only been a small number of families reported with GREM1 mutations and HMPS, therefore the clinical features are not well known. In general, HMPS increases the risks of developing multiple polyps at a younger age and for developing colorectal cancer.

MITF
(3p13)

Certain mutations in the MITF gene may increase the risk for an individual to develop kidney (renal) cancer and melanoma (skin cancer).

MLH1
(3p22.2)

Approximately 50% of Lynch syndrome cases with an identified mutation are due to mutations in the MLH1 gene. Lynch syndrome is also called hereditary non-polyposis colorectal cancer (HNPCC). This diagnosis holds increased risk to a variety of cancer types including cancers of the colorectal tract, stomach, small bowel, hepatobiliary tract, urinary tract, brain, skin, and in females ovarian and endometrium.

Individuals with two copies of the MLH1 mutation can have a condition that is referred to as constitutional mismatch repair deficiency (CMMR-D). Individuals with CMMR-D have early onset childhood colorectal cancer, cancers of the blood (leukemia or lymphoma), noncancerous tumors that grow along nerves (neurofibromas) and café-au-lait spots.

MRE11A
(11q21)

Some mutations in MRE11A could be associated with a higher risk of breast and ovarian cancer.

Mutations in this gene can also result in Ataxia-Telangiectasia-like disorder which is an autosomal recessive disorder that is characterized by progressive cerebellar degeneration, resulting in ataxia and oculomotor apraxia.

MSH2
(2p21-p16.3)

Approximately 40% of Lynch syndrome cases with an identified mutation are due to mutations in the MSH2 gene. Lynch syndrome is also called hereditary non-polyposis colorectal cancer (HNPCC). This diagnosis holds increased risk to a variety of cancer types including cancers of the colorectal tract, stomach, small bowel, hepatobiliary tract, urinary tract, brain, skin, and in females ovarian and endometrium.

Individuals with two MSH2 mutations can have a condition that is referred to as constitutional mismatch repair deficiency (CMMR-D). Individuals with CMMR-D have early onset childhood colorectal cancer, cancers of the blood (leukemia or lymphoma) and noncancerous tumors that grow along nerves (neurofibromas) and café-au-lait spots.

MSH6
(2p16.3)

Mutations in the MSH6 gene have been reported in about 10% of families with Lynch syndrome that have an identified gene mutation. Lynch syndrome is also called hereditary non-polyposis colorectal cancer (HNPCC). This diagnosis holds increased risk to a variety of cancer types including cancers of the colorectal tract, stomach, small bowel, hepatobiliary tract, urinary tract, brain, skin, and in females ovarian and endometrium.

Individuals with two MSH6 mutations can have a condition that is referred to as constitutional mismatch repair deficiency (CMMR-D). Individuals with CMMR-D have early onset childhood colorectal cancer, cancers of the blood (leukemia or lymphoma) and noncancerous tumors that grow along nerves (neurofibromas) and café-au-lait spots.

MUTYH
(1p34.1)

Having two mutations in the MUTYH gene, one from each parent causes MUTYH -associated polyposis or MAP. Adults who are affected have a high risk of developing colorectal polyps. The risk of colorectal cancer is very high regardless of the number of polyps a person has. MAP also increases the risk for other types of cancer including duodenal, and to a lesser extent ovarian, bladder, breast, endometrial, skin, and thyroid.

People with a single mutation of the MUTYH gene do not have MAP, however, they may have a small increase in risk for colorectal cancer, especially if they have a family history of colon cancer.

NBN
(8q21.3)

Women who have a single mutation in the NBN gene may have an increased risk for breast cancer and possibly ovarian cancer, whereas males with a mutation in this gene may be at increased risk for prostate cancer. Additionally, mutations in this gene may increase the risk for other cancers such as colorectal, pancreatic, hematologic and gastric. The specific increased risks are not known.

Nijmegen breakage syndrome (NBS) occurs when an individual inherits two NBN mutations. NBS is a progressive rare condition that causes slowed growth, small head size, recurrent infections, intellectual disability, and an increased risk for cancer.

NF1
(17q11.2)

Mutaitons in the Neurofibromatosis type 1 (NF1) gene are associated with an increase risk of breast cancer.

NF1 is a condition characterized by changes in skin coloring (pigmentation) and the growth of tumors along nerves in the skin, brain, and other parts of the body. The signs and symptoms of this condition vary widely among affected people.

PALB2
(16p12.2)

Women with a mutation in the PALB2 gene are at an increased risk for breast cancer and ovarian cancer. Men may be at increased risk for male breast cancer. For both men and women, there is also an increased risk for pancreatic cancer.

Individuals with two mutations in PALB2 mutation, one from each parent, would be affected with Fanconi anemia (type N). Fanconi anemia is a rare condition that can cause bone marrow failure, skeletal abnormalities, and an increased risk of certain childhood cancers.

PMS2
(7p22.1)

Mutations in the PMS2 gene have been reported in < 5% of families with Lynch syndrome that have an identified gene mutation. Lynch syndrome is also called hereditary non-polyposis colorectal cancer (HNPCC). This diagnosis holds increased risk to a variety of cancer types including cancers of the colorectal tract, stomach, small bowel, hepatobiliary tract, urinary tract, brain, skin, and in females ovarian and endometrium.

Individuals with two PMS2 mutations can have a condition that is referred to as constitutional mismatch repair deficiency (CMMR-D). Individuals with CMMR-D have early onset childhood colorectal cancer, cancers of the blood (leukemia or lymphoma) and noncancerous tumors that grow along nerves (neurofibromas) and café-au-lait spots.

POLD1
(19q13.33)

Individuals with a mutation in the POLD1 gene have an increased chance to develop multiple colorectal polyps, colorectal cancer, and possibly other types of cancer.

POLE
(12q24.33)

Individuals with a mutation in the POLE gene have an increased chance to develop multiple colorectal polyps, early onset colorectal cancer, and possibly other types of cancer.

PTEN
(10q23.31)

PTEN mutations cause PTEN Hamartoma Tumor Syndrome, which has a variety of other names as well. People with a PTEN mutation are at increased risk for female breast, colorectal, endometrial, skin, and other types of cancer. Individuals with a mutation in PTEN regardless of gender may develop noncancerous tumor-like growths, throughout the body, called hamartomas.

Some people with a PTEN mutation have a syndromic diagnosis, which may be Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, or Lhermitte-Duclos syndrome. As such, if a person is identified to have a PTEN mutation, a thorough medical history and physical exam may be warranted.

RAD50
(5q31.1)

Mutations in the RAD50 gene may be associated with a higher risk for breast and ovarian cancers but the data is unclear. Mutations may also contribute to polycystic ovary syndrome.

RAD51C
(17q22)

Women who have a mutation in RAD51C may be at increased risk to develop ovarian cancer and possibly breast cancer. It is currently unclear if men who have a mutation in this gene are at increased risk for cancer, or in general if there is a predisposition to other cancer types. There is limited information about mutations in this gene and its associated cancer risks.

Individuals with two mutations in RAD51C can be affected with Fanconi anemia (FA). FA is a rare condition that can cause bone marrow failure, skeletal abnormalities, and an increased risk of certain childhood cancers. In rare cases, symptoms do not occur until early adulthood.

RAD51D
(17q12)

Women who have a mutation in RAD51D are at increased risk to develop ovarian cancer and possibly breast cancer, but the data is currently unclear. Men with a mutation in this gene are at increased risk to develop prostate cancer.

SMAD4
(18q21.2)

Individuals who have a single mutation in SMAD4 can have juvenile polyposis syndrome (JPS), which results in multiple noncancerous growths called juvenile polyps. These can lead to anemia. There is an increased risk to develop colorectal cancer, and possibly stomach, pancreatic and bile duct cancer. In addition, affected individuals have an increased risk for hereditary hemorrhagic telangiectasia (HHT) and the associated characteristics.

STK11
(19p13.3)

Having a single mutation in STK11 causes Peutz-Jeghers syndrome (PJS). PJS is characterized by gastrointestinal polyposis, mucocutaneous pigmentation, and cancer predisposition. People with PJS are at increased risk for colorectal, stomach, small bowel, pancreatic, and lung cancers. Additionally, women are at increased risk for breast, ovarian, cervical and uterine cancer and men are at increased risk for testicular cancer.

TP53
(17p13.1)

People with TP53 mutations have Li-Fraumeni syndrome (LFS). LFS leads to an increased risk of developing soft tissue sarcoma, osteosarcoma, female breast cancer, brain tumors, adrenocortical carcinoma (ACC), leukemia, and potentially other types of cancer as well. The age of onset of cancers in LFS is quite young. Many people with LFS develop multiple primary cancers.

Last Updated: July 31, 2019

Legend
Increased risk to potential increased risk
Uncertain presumed high risk
Unknown or insufficient risk

* The information provided is a guide to the cancers that have been associated in the scientific literature with mutations in the genes listed. Surveillance recommendations regarding mutations found in any of these genes are provided by the NCCN Clinical Practice Guidelines in Oncology.

Cimmino F., et al, Dualistic Role of BARD1 in Cancer. Genes. 2017, 8 (12), 375-398
Cotterill SJ. BLM, Cancer Genetics Web: http://www.cancer-genetics.org/BLM.htm Accessed: Tue Jul 30 2019
Golmard L., et al. Germline mutation in the RAD51B gene confers predisposition to breast cancer. BMC Cancer 2013; 13:484
Hallamies S., et al. CHEK2 c.1100delC mutation is associated with an increased risk for male breast cancer in Finnish patient population. BMC Cancer. 2017; 17: 620
Honglin S., et al. Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population. J Clin Oncol. 2015; 33(26), 2901-2907
Leachman S. A., et al. Identification, genetic testing, and management of hereditary melanoma. Cancer Metastasis Rev. 2017; 36:77–90
Lieberman S., et al. Features of Patients With Hereditary Mixed Polyposis Syndrome Caused by Duplication of GREM1 and Implications for Screening and Surveillance. Gastroenterology. 2017; 152:1876–1880
Masoomian B., et al. Overview of BAP1 cancer predisposition syndrome and the relationship to uveal melanoma. Journal of Current Ophthalmology. 2018, 30, 102-109
National Comprehensive Cancer Network Guideline in Oncology, Genetic/Familial High-Risk Assessment: Breast and Ovarian Version 3.2019-January 18, 2019
National Comprehensive Cancer Network Guideline in Oncology, Genetic/Familial High-Risk Assessment: Colorectal Version 1.2019-July 3, 2019
Penkert J., et al. Breast cancer patients suggestive of Li-Fraumeni syndrome: mutational spectrum, candidate genes, and unexplained heredity. Breast Cancer Research. 2018; 20:87: doi.org/10.1186/s13058-018-1011-1
Puntervoll H.E., et al. Melanoma prone families with CDK4 germline mutation: phenotypic profile and associations with MC1R variants. J Med Genet. 2013; 50:264–270
Ramus S. J., et al. Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer. J Natl Cancer Inst. 2015; 107(11): djv214. http://doi.org/10.1093/jnci/djv214
Rosner G., et al. POLD1 and POLE Gene Mutations in Jewish Cohorts of Early-Onset Colorectal Cancer and of Multiple Colorectal Adenomas. Diseases Of The Colon & Rectum Volume. (2018) 61(9), 1073-79
Wang A., et al. BAP1: gene of the month. J Clin Pathol 2016;69:750–753

Hereditary Cancer Results – What Does It Mean?

Positive Result - indicates that a change or mutation in the genetic code has been identified which is associated with an increased risk for hereditary cancer. This result does not mean that you currently have cancer or will develop cancer in the future.

Negative Result - indicates that no mutation in the genes tested was identified, however; this test does not completely rule out your lifetime risk of developing cancer.

Variant Of Uncertain Significance (VUS) - indicates a change in the genetic code has been identified, however based on current knowledge and clinical data, it is not known if this is a normal genetic variant or a mutation associated with an increased risk for cancer. Further analysis may be recommended, including testing other family members or obtaining more information about you and your family history, to assist in determining whether or not the identified VUS will pose a greater than average risk for you to develop cancer.

Frequently Asked Questions

Testing

Usually, all of the DNA in your saliva sample is used to obtain your genetic results. We may retain and store left over DNA for up to sixty days in case a re-test is necessary.

No. ScionGenomics hereditary cancer testing is only available for people 18 years old or older. Because of concerns about privacy and autonomy, professional societies like the American Academy of Pediatrics discourage genetic testing for adult-onset conditions in minors.

Family members (over age 18) who are related to you and have a positive personal or family history of cancer may be eligible for testing. They should discuss this with their health care provider or contact a genetic counselor. To find a genetic counselor click here.

If you received bone marrow from a donor, then some of the cells of your body will contain the donor's genetic material (DNA). Therefore, genetic testing on your saliva sample may produce a result that is actually from the DNA of your donor. This would not apply if you used your own bone marrow for the transplantation.

Information about the 35 hereditary cancer genes that are to be tested can be found on our web site. Learn More

No. The ScionGenomics test is not designed to test for paternity, however; in some cases, if individuals within the same family are tested it is possible that an issue of relatedness may be revealed.

No, only about 5% to 10% of cancers are thought to be the result of an inherited mutation. The vast majority of cancer is sporadic, which means there are gene mutations in the tumor cells but not in other healthy cells.

Sample

Yes, your doctor must authorize and order cancer genetic testing before we can proceed. When we receive a signed requisition form from your doctor, he or she may request that we send a sampling kit directly to your home.

A saliva sample is required for testing. If your doctor orders testing, he or she may request we send a sampling kit directly to your home. The sampling kit includes directions on how you collect a sample of your saliva, the sampling container, labels, the consent form and a package with return postage ready for shipping. A video is available on how to collect the sample on our web site. Watch Video

If your doctor requests we send the sampling kit directly to your home, there will be detailed instructions in the sampling kit. These instructions are also available on the ScionGeneomics web site There is also an easy to follow video on the ScionGenomics web site. Watch Video

No, but the sooner the package is shipped the quicker we can receive your sample for testing. If you are unable to have it shipped right away the sample can be kept at room temperature for several days.

Yes, but this is unlikely. In some cases, we may need to ask you for another sample to be sent, but this is unlikely. This is normally caused by additional substances mixed with your saliva, such as food, or not enough saliva to obtain an adequate amount of DNA for testing.

Results

Your test results will be available in approximately 4 weeks after the laboratory receives your saliva sample.

The health care provider that ordered your test will receive a copy of your results via email. You will also get a copy of your results in the mail or via email 20 days after the results have been sent to your provider.

You should receive your results from the health care provider that ordered your testing. You will also receive a copy of your results in the post or by email 20 days after the results have been sent to your provider.

ScionGenomics has board certified genetic counselors that are available to discuss your genetic testing results. You can have a ScionGenomics genetic counselor contact you by emailing [email protected] or calling (954) 715-5040.

This is up to you. If you are found to carry a cancer genetic mutation, your family members are at increased risk of having that mutation as well. If you don’t carry a mutation, your family members are at decreased risk of carrying that mutation, though not zero. Therefore, your genetic testing results may be useful to your family members.

If you have a family member who has a cancer genetic mutation, it is important to find out what genetic mutations he or she has and inform your health care provider. If your family member’s mutation is one that we test for, negative results from ScionGenomics would rule out that specific mutation in you. On the other hand, if it is a mutation that we do not test for, additional testing for that specific known mutation would be indicated. This testing would be ordered through your health care provider. View the Hereditary Cancer Genes Page

If you are found to have a mutation that increases your risk for cancer your doctor would advise you regarding preventative measures that can reduce your risk, you would be offered preventative screening tests to detect cancer at an earlier and more treatable stage and finally such information may be helpful to your close family members who may also choose to have testing.

Health Insurance / Privacy

Yes. Health insurance companies do not automatically receive a copy of your genetic testing results from ScionGenomics; however, if we invoice your health insurance company and they request your records as part of an audit, then we are must send a copy to them.

Unlikely. GINA (Genetics Information Non-discrimination Act) makes it illegal for most health insurance companies to make policy decisions based on genetic test results alone. This does not apply to life or long-term insurance. (Learn more about GINA).

HIPAA (Health Insurance Portability and Accountability Act) ensures the protection, privacy and security of your health information. Learn More About HIPPA

Introduction to Genetics
View Introduction to Genetics

Saliva (DNA) Collection Instructions