INHERITED CANCER SCREENING - Genomics For Life
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Focusing on
Personalised Medicine
INHERITED CANCER SCREENING
Inherited genetic mutations can be passed down from parents to their children and cause between 5 to 10% of all cancers.
Families with a strong history of cancer may have a genetic mutation that has been passed through the generations leading to
a higher rate of cancer within the family, than in the general population.
Some families may have a history of cancer due to a shared environment or lifestyle, such as tobacco use, obesity or sun
exposure, which may not be due to a genetic pre-disposition. However, certain patterns in a family — such as the types of
cancer that develop, other non-cancer conditions that are seen, and the ages at which cancer develops — may suggest the
presence of an inherited cancer syndrome. Genetic tests can indicate if there is a genetic predisposition for cancer within a
family and can help predict which family members are most at risk.
If a genetic mutation is present in a family, not everyone who inherits the mutation will necessarily develop cancer. However,
Genomic Testing for Inherited Cancer Syndromes can empower patients with the knowledge to take control of their health and
be aware of their lifetime risk of cancer, enabling earlier detection and treatment.
Common Inherited Cancer Syndromes
Hereditary Breast and Ovarian Cancer Lynch Syndrome
Hereditary breast and ovarian cancer (HBOC) resulting from Lynch syndrome is characterized by an increased risk for
mutations in the BRCA1 and BRCA2 genes occurs in all ethnic colorectal cancer and cancers of the endometrium, stomach,
and racial populations. BRCA mutations increase the risk ovary, small bowel, hepatobiliary tract, urinary tract, brain,
of developing breast and ovarian cancer, and patients with and skin. [9] In individuals with Lynch syndrome the following
mutations tend to develop breast cancers at a younger age. lifetime risks for cancer are seen:
Around 1 in 400 people are believed to have BRCA1 or BRCA2 • Colorectal Cancer: 52%-82%
mutations and 5 – 10% of breast cancers result from a • Endometrial cancer in females: 25%-60%
mutation in the BRCA1 and BRCA2 genes. [1-4] Men with BRCA • Gastric cancer: 6% to 13% for gastric cancer
mutations have a higher risk of prostate cancer and are also • Ovarian cancer: 4%-12%
at increased risk of breast cancer. [5,6] Men and women with
BRCA mutations may be at increased risk of pancreatic and Neurofibromatosis type 2
stomach cancer. [7,8] Neurofibromatosis type 2 is a tumour prone disorder
characterised by the development of benign (non-cancerous)
Von Hippel Lindau syndrome tumours known as schwannomas and meningiomas. [13]
Von Hippel-Lindau (VHL) syndrome is an inherited disorder Although these tumors are benign, they can cause hearing
characterized by the formation of tumors and cysts in many and balance problems and other significant medical
different parts of the body, including hemangioblastomas of problems, especially if there are multiple tumours in or next
the brain, spinal cord, and retina; renal cysts and clear cell to the brain. The average age of onset is 18 to 24 years and
renal cell carcinoma; pheochromocytoma, pancreatic cysts, almost all affected individuals develop tumours by age 30
and neuroendocrine tumours; endolymphatic sac tumours; years.
and epididymal and broad ligament cysts. [12] Tumors may Li-Fraumeni syndrome
be cancerous or noncancerous and most frequently appear Li-Fraumeni syndrome is associated with high lifetime risks
during young adulthood; however, the signs and symptoms of cancer. The risk of cancer is estimated at 50% by age 30
of von Hippel-Lindau syndrome can occur throughout life. years and 90% by age 60 years. [10] Within families whose
Retinal hemangioblastomas may be the initial manifestation members have Li-Fraumeni syndrome, the prevalence of
of VHL syndrome and can cause vision loss. Renal cell specific malignancies differs during childhood, adolescence,
carcinoma occurs in about 70% of individuals with VHL and is and adulthood. [11] The most common cancers observed
the leading cause of mortality. [12] in families with Li-Fraumeni syndrome include soft tissue
sarcomas, brain tumours, adrenocortical carcinoma, bone
sarcomas and breast cancer.
Toll Free: 1800 445 433 Fax: 1300 658 893
Email: patientcare@genomicsforlife.com.au Web: www.genomicsforlife.com.au
Focusing on
Personalised Medicine
How can Genomic Testing Benefit Me?
Genomic Testing for Inherited Cancer Syndromes empowers patients to take control of their health and be aware of their
lifetime risk of cancer, enabling earlier detection and treatment. Patients can be tested for Inherited Cancer Syndromes
whether they are currently diagnosed with cancer or not.
If currently diagnosed with cancer, Inherited Cancer Screening can be performed along with other genetic testing to see if other
members of your family, such as your children, may be at higher risk of developing cancer.
If not currently diagnosed with cancer, patients can still be assessed to see if they are at an increased risk of developing
certain cancers enabling them to:
• Start cancer screening tests earlier
• Get screened for that type of cancer more often
• Get access to screening tests that are used only for people known to be at increased cancer risk
• Watch yourself closely for signs or symptoms of that kind of cancer
• Learn about options to help reduce the risk of certain types of cancer, such as drugs or surgery
What Testing Options are Available?
Inherited Cancer Panel BRCA Testing
• Over 200 hereditary cancer susceptibility syndromes • Our BRCA Test screens for inherited mutations in
have been described. the BRCA1 and BRCA2 genes, as well as ATM, CDH1,
• Our panel looks at 42 genes implicated in some RAD51C, CHEK2, RAD51D, NBN, RAD51L3-RFFL,
of the most common inherited cancer syndromes SMARCA4 and TP53
including: Hereditary breast and ovarian • Around 5 – 10 % of breast cancers result from a
cancer (BRCA1/BRCA2), Li-Fraumeni syndrome mutation in the BRCA1 and BRCA2 genes. BRCA
(TP53), Lynch Syndrome (MLH1/MSH2/MSH6/ mutations increase the risk of developing breast and
PMS2), Von Hippel Lindau syndrome (VHL) and ovarian cancer, and patients with BRCA mutations
Neurofibromatosis 2 (NF2). tend to develop breast cancers at a younger age.
How Do I Organise Testing?
Genomics For Life aims to educate patients and their families on their cancer type and empower them with the knowledge to
take control of their treatment plans. As each patient’s case is unique, there is no “one size fits all” when it comes to testing.
We encourage you to contact Genomics For Life, and we can work with you and your oncologist/specialist, to determine what
tests would benefit you.
Download Request Receive testing kit Genomics For Life Genomics For Results sent to
Form and complete from Genomics Receives sample Life completes nominated health
and return to for Life for testing requested testing care professional
Genomics For Life
References
1. Ford, D., D. F. Easton, et al. (1994). “Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium.” Lancet 343(8899): 692-695.
2. Claus, E. B., J. M. Schildkraut, et al. (1996). “The genetic attributable risk of breast and ovarian cancer.” Cancer 77(11): 2318-2324.
3. Whittemore, A. S. (1997). “Risk of breast cancer in carriers of BRCA gene mutations.” N Engl J Med 337(11): 788-789.
4. Whittemore, A. S., G. Gong, et al. (1997). “Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: results from three U.S. population-based case-control studies of ovarian cancer.” Am J Hum Genet 60(3):
496-504.
5. Levy-Lahad, E. and E. Friedman (2007). “Cancer risks among BRCA1 and BRCA2 mutation carriers.” Br J Cancer 96(1): 11-15.
6.Tai, Y. C., S. Domchek, et al. (2007). “Breast cancer risk among male BRCA1 and BRCA2 mutation carriers.” J Natl Cancer Inst 99(23): 1811-1814.
7. Ferrone, C. R., D. A. Levine, et al. (2009). “BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma.” J Clin Oncol 27(3): 433-438.
8. Cavanagh, H. and K. M. Rogers (2015). “The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers.” Hered Cancer Clin Pract 13(1): 16.
9. Kohlmann, W. and S. B. Gruber (1993). Lynch Syndrome. GeneReviews((R)). M. P. Adam, H. H. Ardinger, R. A. Pagon et al. Seattle (WA).
10. Schneider, K., K. Zelley, et al. (1993). Li-Fraumeni Syndrome. GeneReviews((R)). M. P. Adam, H. H. Ardinger, R. A. Pagon et al. Seattle (WA).
11. Olivier, M., D. E. Goldgar, et al. (2003). “Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype.” Cancer Res 63(20): 6643-6650.
12. Frantzen, C., T. D. Klasson, et al. (1993). Von Hippel-Lindau Syndrome. GeneReviews((R)). M. P. Adam, H. H. Ardinger, R. A. Pagon et al. Seattle (WA).
13. Zucman-Rossi, J., P. Legoix, et al. (1998). “NF2 gene in neurofibromatosis type 2 patients.” Hum Mol Genet 7(13): 2095-2101.
Dear Doctor, Your patient is exploring genetic testing and has requested Genomics For Life to perform the testing for them. Genomics For Life is a fully NATA accredited, TGA approved, clinical diagnostic laboratory located in Brisbane. It offers a complete range of genomic testing services, including comprehensive inherited disease screening. The service is performed with the support of the patient’s referring Doctor. Our inherited disease testing is performed using Next Generation Sequencing and covers the coding regions of the gene and a small amount of the non-coding parts of the gene. It does not cover all of the non-coding parts (introns, inversions, promoter regions) of the genes. The amount of the gene covered, and the types of mutations depends on the gene itself. Further information may be required to check if a specific mutation is covered by testing. Our assays detect known variants but can also identify unknown variants, as they do not just look for the common/known variants. It does not look at copy numbers where there may be loss of one copy of the gene or an increase in the copies of the gene. A comprehensive report is issued if there are any variants identified that are clinically significant. Pathogenic variants, likely pathogenic variants, and variants of uncertain significance are reported in the specific genes requested for testing. The gene requested will be tested as part of one of our multi-gene panels and as such testing could reveal information unrelated to the patient’s clinical features. Pathogenic variants and likely pathogenic incidental findings in the genes screened on the multi-gene panel will always be reported back to the referring clinician. If you require a list of the genes associated with a particular panel, please contact us. The genes are also screened as per the ACMG guidelines and likely deleterious and pathogenic mutations in the relevant genes, if included on the multi-gene panel, are reported. A full list of ACMG genes is available here: https://www.ncbi.nlm.nih.gov/clinvar/docs/acmg/ It is assumed that the patient has been appropriately counselled by the referring clinician or genetic counsellor about the nature of the test and potential incidental findings this multi-gene panel may reveal. If you require a referral for a genetic counsellor for the patient, please contact Genomics For Life. Genetic counselling can be arranged for your patient, by health care professionals that are conversant in genetic testing. Additional information is available on our website: www.genomicsforlife.com.au, including details on our comprehensive testing menu. The FAQ’s contain more information on how Genomics testing may assist patient care and details of the processes involved in testing. Prior to proceeding with testing, we encourage the patient to discuss with us their budget and testing options, to ensure that we offer a solution that is both economically viable for the patient and useful for the medical practitioner. If you would like to contact us, to further discuss testing, please don’t hesitate to call us on 1800 444 546 or via email at patientcare@genomicsforlife.com.au Kind regards, Genomics For Life
SOMATIC MUTATION TESTING
REQUEST FORM Accredited for compliance with NPAAC Standards and ISO 15189
NATA Accreditation Number: 19325
PATIENT DETAILS ORDERING MEDICAL PRACTITIONER DETAILS
Patient Surname: Doctor Name:
Patient Given Name(s): Provider Number:
DOB: ____ / ____ / ______ Male Female Practice Name:
Patient Address: Practice Address:
Contact Number: Contact Number:
Email: Fax:
Medicare Details: Email (for results):
PATIENT INFORMED CONSENT STATEMENT MEDICAL PRACTITIONER CONSENT STATEMENT
I agree to the genetic analysis and the release of my tissue and/or other By signing this form, I confirm to the best of my knowledge that I have the
samples for testing. consent of the patient to request somatic and/or germline testing, and
that the patient is aware that this test may require pre-payment prior to
commencement of the test.
Patient’s Signature: Doctor’s Signature:
Date: Date:
PRIVACY NOTE: The information provided will be used to assess any Medicare Beneft payable for the services rendered and
to facilitate the proper administration of government health programs, and may be used to update enrolment records. Its
collection is authorised by provisions of the Health Insurance Act 1973. The information may be disclosed to the Department
of Health and Ageing or to a person in the medical practice associated with this claim, or as authorised/required by law.
CLINICAL INFORMATION
Please attach all relevant patient history and pathology reports Metastatic Disease: Yes No
TEST(S) REQUESTED
Comprehensive Plus Solid Tumour Analysis TSP 23TM : Melanoma, Lung & Bowel Cancer Targeted Assay
Transcriptome Analysis Inherited Cancer Assay
Tumour Mutational Burden Assay Cell-Free DNA Testing (dPCR - Single Probe)
Sarcoma Assay Cell-Free DNA Assay
PanCancer Assay Lung Assay
Homologous Recombination Deficiency (HRD) Assay Colon Assay Breast Assay
BRCA Somatic Assay Pharmacogenomics
BRCA Germline Assay Other:
Please complete all the above fields. Once the Test Requesition Form has been completed, please return to Genomics For Life along with the sample. Patient
must sign consent form to perform the test.
Billing Information Collection Staff Only Laboratory Use Only
NOTE 1: Payment must be cleared prior to testing being performed, unless Medicare rebateble. Collection Sample Rec. Sample Type:
NOTE 2: There may be out-of-pocket expenses for retrieval of slides imposed by other laboratories that may Date: Type: Date: (Exp Date)
be charged to the patient.
NOTE 3: Laboratory will contact you prior to the commencement of testing to arrange payment. Credit card Collection Collector’s Rec. Rec.
payments will incur a surcharge. Direct Debit option is available. Time: Signature Time: By:
GFLADM-1222307366-204
Phone: 1800 445 433 Fax: 07 3054 4363 Email: patientcare@genomicsforlife.com.au Mail: PO Box 1201 Milton QLD 4064 Version: 4.0
Review Date: 24/05/2023SOMATIC MUTATION TESTING
REQUEST FORM Accredited for compliance with NPAAC Standards and ISO 15189
NATA Accreditation Number: 19325
TESTING OPTIONS SAMPLE TYPE
Comprehensive Plus Solid Tumour Analysis - Targeted sequencing (NGS) assay that enables the detection of relevant SNVs,
CNVs, gene fusions, and indels from 500 unique genes. Also includes Tumour Mutational Burden, Homologous Recombination Tissue
Deficiency and Microsatellite Instability.
Transcriptome Analysis - This assay assesses the mRNA expression of 20809 genes which can provide complementary
information to DNA testing. Integrative sequence analysis provides a clinically relevant, multi-dimensional view of the complex
molecular landscape and microenvironment of cancers. Gene expression profiles help assess the functional status of critical
pathways. Specific mutations in cancer-associated pathway genes, like those of the NOTCH, WNT–beta-catenin, SHH (sonic hedgehog Tissue
gene), and HIPPO pathways, can be assessed for functional consequences in terms of expression levels of their downstream target
genes. This type of testing has been shown to potentially increase the number of targetable pathways and provide prognostic
information and improve classifications of tumours.
Tumour Mutational Burden - Our report collates available information, previously identified through histology and PD-L1 staining,
Tissue
combined with genetic analysis of 409 cancer driver genes, to provide a likelihood of response to Immune Checkpoint Inhibitors.
Sarcoma Assay - The Sarcoma Assay is a targeted sequencing assay that simultaneously detects and identifies gene fusions
associated with soft tissue cancers. This panel is particularly useful in correctly diagnosing potential sarcoma tumours which then can Tissue
correctly identify possible drug targets for treatment.
Homologous Recombination Deficiency (HRD) Assay - Includes analysis of genes associated with HRD and HRR pathways,
Tissue
including BRCA1, BRCA2, ATM, CHD1, CHEK2, NBN, PALB2, RAD51C, RAD51D, RAD51L3-RFFL, SMARCA4 and TP53 genes.
TSP 23TM: Melanoma, Lung & Bowel Cancer Targeted Assay - Targeted Sequencing Panel covering 23 genes involved in lung
Tissue
cancer, bowel cancer and melanoma. Does not include CNVs or Tumour Mutational Burden. (Medicare Rebate may apply)
Kids Cancer Targeted Therapy Assay - Includes a large 97-gene translocation/fusion panel, as gene fusions and copy number
alterations are more common in childhood cancers. Also includes an 82-DNA target panel with comprehensive coverage of all relevant
mutations, 44 targets with full exon coverage, specifically tumour suppressor genes, and 24 CNV targets, including several key driver Tissue
DNA mutations that have been described in different paediatric tumours. This panel can also be used for adult tumours depending on
the tumour type.
BRCA Plus Assay - Includes analysis of BRCA1 & BRCA2, as well as 9 other genes commonly associated with Breast and Ovarian
Cancers - ATM, CHD1, CHEK2, NBN, PALB2, RAD51C, RAD51D, RAD51L3-RFFL, SMARCA4, TP53
Tissue or Blood
• Germline (Blood) - Includes NGS and MLPA on BRCA1 and BRCA2 (Medicare Rebates may apply)
• Somatic (Tissue) - NGS Only (No Medicare Rebate available)
Inherited Cancer Panel - Various Multi-gene panels specific for Pancreatic, Breast, Ovarian, Endometrial and Colorectal Cancers
Blood
including CNV (Medicare rebates may apply)
Pharmacogenomics - Comprehensive Analysis of 40 drug metabolism enzymes designed to give information on metabolism of all
Blood
drug classes including oncology drugs. This can indicate the likelihood of an adverse drug reaction.
TCR-Beta Assay - T-cells can recognise foreign particles through their T-cell receptors (TCRs), which have variable ends enabling the
recognition of millions of foreign molecules. This test looks at all the different T-cell receptors in the patient’s sample (TCR repertoire),
assessing diversity and clonal expansion. This can determine how your immune system is recognising and responding to the cancer.
Tissue or Blood
The assay can be used to assess if the immune system is recognising the tumour and generating more cells directed at fighting the
tumour. This test can be used on a blood sample or a tumour tissue sample and follow up testing can help determine if immune
checkpoint inhibitors are working. This is a measure of what is occurring in the patient rather than a prediction of what may occur.
Cell-Free assays are useful for early detection of relapse & response to therapy. Cell-Free assays an also be used when tissue biopsy is
not an option. This testing can identify mutations at levels below 1%
cfDNA™ (dPCR) - Mutation Tracking analysis using blood samples – eg EGFR T790M. Other single point known mutations are
Blood
available - please contact us for further information.
Cell-Free DNA PanCancer Assay - The analysis of 52 genes and 96 fusions. Includes CNVs for 12 genes, such as EGFR and MET.
Changes in cell-free DNA occur in response to therapy including immune checkpoint inhibitors and this test can aid in evaluating Blood
response.
Cell-Free DNA Lung Assay - 12 genes found in lung cancer including genes associated with resistance including RET, ALK and
Blood
ROS-1 fusions and CNVs, MET including exon 14 skipping
Cell-Free DNA Breast Assay - 12 genes including CNVs for CCND1, ERBB2 and FGFR1 Blood
Cell-Free DNA Colon Assay - 14 genes including AKT1, APC, BRAF, CTNNB1, EGFR, ERBB2, FBXW7, GNAS, KRAS, MAP2K1, NRAS,
Blood
PIK3CA, SMAD4, TP53
For further information on our available tests, please contact Genomics For Life or visit our website. If you are unsure which test(s) are best
suited for your patient, please contact Genomics For Life and we can help determine which test(s) would be beneficial for their particular clinical
circumstances.
GFLADM-1222307366-204
Phone: 1800 445 433 Fax: 07 3054 4363 Email: patientcare@genomicsforlife.com.au Mail: PO Box 1201 Milton QLD 4064 Version: 4.0
Review Date: 24/05/2023You can also read
