BrainTumorNext

Genetic testing for hereditary brain tumors patient guide

Brain Tumor Facts • Fewer than 1% of people in the U.S. will be diagnosed with a brain tumor/cancer in his or her lifetime • The most common tumor/cancer in children and young adults (0-19 years old) and the 16th most common tumors/cancers in adults • Brain tumors/cancer diagnosed at a younger age may suggest the possibility of hereditary cancer

causes of brain tumors Familial: may be due to genes and/or shared factors, such as environment and lifestyle Hereditary: due to inherited genetic changes; there are many genes known to cause hereditary brain tumors/cancer

Sporadic: happens in one person, or possibly two distantly related family members, at older ages

What are Hereditary Brain Tumors? Although many people have a family history of cancer, the majority of primary brain tumors are not hereditary. Currently, it is unclear what percent of primary brain tumors diagnosed each year are hereditary, and more research needs to be done in this area. People with hereditary brain tumors develop them because of a change (or mutation) in a gene. Individuals who carry these mutations are born with them – they do not develop over time. Understanding if brain tumors are due to an inherited mutation can help clarify your/your family member’s future risks to develop cancer/tumors. It can also help determine your/your family member’s options for cancer and other medical screening and/or prevention.

BrainTumorNext Genes and Associated Risks GENE

ASSOCIATED CANCER/TUMOR(S)

AIP

Pituitary adenoma (>50%)

ALK

Nerve tumors, possibly medulloblastoma

APC

Colorectal (up to 100%), pancreatic, medulloblastoma, other

CDKN1B

Hyperparathyroidism (~100%), pituitary adenoma, other

CDKN2A

Melanoma (28-67%), pancreatic (17-25%), astrocytoma

DICER1

Pleuropulmonary blastoma, cystic nephroma, brain, other

Parathyroid (>90%), GEP tumors (30-70%), pituitary adenoma (30-60%), adrenal (15-50%), other MLH1 , MSH2, Colorectal (up to 82%), uterine (up to 60%), stomach (6-13%), MSH6, PMS2 ovarian (4-12%), gliomas, prostate, other Vestibular schwannomas (>90%), other schwannomas (24NF2 51%), meningiomas (45-58%), spinal tumors (63-90%) MEN1

NBN

Breast, medulloblastoma, ganglioglioma, prostate, other

NF1

Female breast, malignant nerve sheath tumors (8-13%), optic glioma, astrocytoma, other

PHOX2B

Nerve tumors

POT1

Gliomas

PRKAR1A

Primary pigmented nodular adrenocortical disease (26-60%), pituitary adenoma (10-12%), myxomas (up to 53%), thyroid nodules (25%), schwannomas (8-10%), other

PTCH1

Basal cell carcinomas, medulloblastoma, sarcoma, other

PTEN

Breast (25-85%), thyroid (10-35%), uterine (5-28%), other

SMARCA4

Ovarian, brain, other

SMARCB1

Atypical teratoid/rhabdoid tumors of nervous system/kidney, schwannomatosis, other

SMARCE1

Meningioma

SUFU

Basal cell carcinomas, jaw keratocysts, medulloblastoma, other

TP53

Breast, sarcoma, brain, adrenocortical, leukemia, other

TSC1 /TSC2

Kidney (2-5%), brain and spine, skin, liver, lung, heart

VHL

Kidney (25-70%), hemangioblastomas (brain and spine), other

GEP tumors: gastro-entero-pancreatic tumors. These include gastrinomas, insulinomas, vasoactive intestinal peptide-secreting tumors (VIPomas), and glucagonomas.

Possible Genetic Test Results If you or your family member has genetic testing, you will receive one of three possible results: RESULTS

EXPLANATION

Positive

• A mutation was found in one of the genes tested • Increased risk for the specific cancer(s), tumors, and other medical issues related to the gene that has a mutation (see previous page) • Medical screening will be recommended specific to the gene that has a mutation • Family members may be tested to find out if they carry the same mutation

Negative

• No changes, or mutations, were found in any of the genes tested • Future cancer/tumor risks are based on personal and/or family history • Medical screening will be based on family history • Genetic testing most likely will not be appropriate for family members, unless they have a personal history suggestive of hereditary cancer. Discuss with your healthcare provider for more information.

Variant of Unknown Significance (VUS)

• A genetic change was found but it is unclear if this change causes increased risk for cancer or not • Cancer/tumor risk(s) is based on personal and/or family history • Medical screening will be based on family history

How Can Genetic Testing Benefit Me and My Family Members? Genetic test results may offer you: • The ability to adjust screening options, such as the age you need to begin and what types may be recommended for you • If a mutation is found in you, your close relatives (like your parents, brothers, sisters, children) have a 50/50 random chance of also testing positive for the same mutation

Has genetic mutation

No mutation

Test Result and Recommendations To be completed by you and your healthcare provider when you receive your/your family member’s genetic test results and medical management recommendations

test result No mutation detected Positive for a mutation in ___________________ gene VUS in ________________________ gene

recommendations for you

recommendations for family members Genetic testing not appropriate for family members Genetic testing recommended for family members

FAQs About Genetic Testing q1. how does braintumornext genetic testing work? Your/your family member’s sample (blood or saliva) is collected using a special kit that is shipped overnight to Ambry. Once the sample arrives at Ambry, 27 genes are studied to look for any mutations that may cause an increased risk for certain cancer/tumors.

q2. can genetic test results be used against me? In the U.S., the Genetic Information Nondiscrimination Act (2008) prohibits discrimination by health insurance companies and employers based on genetic information. Depending on where you live in the world, you may have different laws in this area.

q3. if i have already had a brain tumor, do i need genetic testing? Genetic testing is most informative when first performed in a person who has already had a brain tumor/cancer. Results can provide an explanation for why the cancer/tumor occurred, and, more importantly, can provide information about future cancer/tumor risks. Genetic test results can change your ongoing medical management and help your family members understand their risk of developing cancer/tumors.

q4. what is ambry’s billing policy? Ambry offers a variety of payment options. Many insurance plans cover genetic testing and Ambry is contracted with the majority of U.S. health plans. Your out-of-pocket cost may vary based on your individual plan. We offer personalized verification of insurance coverage and financial options for your genetic testing. A team of dedicated specialists is available to help you get access to the genetic testing you need and answer any questions you have about our payment options. Call or email our Billing department at +1-949-900-5795 or [email protected] with any questions.

q5. what is an explanation of benefits (eob)? It is not a bill and does not require payment. Your insurance company sends you an EOB to explain any services paid on your behalf. You can contact us directly to speak with a Billing specialist with any questions/ concerns about your EOB. Some genetic tests take weeks to process to receive the best results. In addition, insurance companies can take over two months to process claims, and longer if we need to send information again, and this could delay your bill.

Resources for Patients and Families These and other resources can help build a sense of community and aid in answering some common questions.

ambry’s patient sites for families patients.ambrygen.com/cancer patients.ambrygen.com/neurology

american brain tumor association abta.org

i’m too young for this! stupidcancer.org

national brain tumor society braintumor.org

genetic information nondiscrimination act information ginahelp.org

Find a Genetic Counselor national society of genetic counselors nsgc.org

canadian association of genetic counsellors cagc-accg.ca

About Ambry Ambry is a genetics-based healthcare company that is dedicated to open scientific exchange so we can work together to understand and treat all human disease faster.

ambry genetics 15 Argonaut Aliso Viejo, CA 92656 USA +1-866-262-7943 [email protected] For more details about these tests, visit ambrygen.com

ambrygen.com

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