Genetic & Hereditary Cancer Testing
Our genetic testing service at Informed Genomics offers a range of hereditary cancer testing options to meet your requirements, from a complete clinical service to research applications. We can provide selected or multiple components of the testing pathway from sample collection, library enrichment, sequencing, bioinformatics, interpretation*, customised clinical reporting and genetic counselling.
*Interpretation is only offered for approved genes. See Table 1 for details on genes that have been approved for clinical interpretation.
When is hereditary cancer testing used?
Hereditary cancer is defined as cancer that has been caused by an inherited genetic variant. Inheriting certain genetic variants does not necessarily mean that cancer will develop, but the lifetime risk is significantly increased, and it is estimated that 5-10% of all cancer cases have a genetic variant that leads to cancer susceptibility.
A genetic cause is suspected when the clinical features or family history include the following, in which case a hereditary cancer panel is recommended:
It is important to note that not all genetic variants that lead to an increased susceptibility to cancer are associated with a family history. At Informed Genomics, we offer our Hereditary Cancer Panel to anyone over 18 years of age who is believed to be at risk of developing cancer, regardless of personal or familial cancer history.
What are the benefits of hereditary cancer testing?
Detect genetic variants associated with a predisposition to certain cancers
Access to genetic counselling to explain test results, associated implications and support networks
Enables patients and family members to make informed choices
Informed Genomics Hereditary Cancer Clinical Service
Our hereditary cancer clinical service at Informed Genomics aims to identify individuals at a higher-than-population risk for hereditary cancer. We offer a range of hereditary cancer panels to study genes associated with the most common hereditary cancers ranging from a comprehensive multi-cancer panel to targeted panels for breast, ovarian, colorectal, prostate, melanoma and pancreatic cancer.
The panels have been expertly curated using current literature and national testing guidelines to maximise clinical actionability, whilst minimising uncertainty. Our routine turnaround time for this testing is 3-4 weeks, however, prioritisation options are available. Please contact us to discuss your requirements.
The final clinical report summarises test results by providing variant interpretation, the implications of the results, and any recommended actions. Full genetic counselling is available for patients to explain test results and the associated implications, and to inform relevant support networks. Click here for further information on the clinical report.
The 31 gene Comprehensive Hereditary Cancer Panel is the flagship panel for Informed Genomics. The full gene list for this panel and the other panel options are shown in table 1 below.
|Comprehensive Hereditary Cancer Panel||APC, ATM1, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK22, EPCAM3, HOXB13, MLH1, MSH2, MSH6, MUTYH, NF1, NTHL1, PALB2, PMS24, POLD1, POLE, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53, VHL|
|Hereditary Breast Cancer Panel||ATM1, BARD1, BRCA1, BRCA2, CHEK22, PALB2, PTEN, STK11, TP53|
|Hereditary Breast and Gynaecological Cancer Panel||ATM1, BARD1, BRCA1, BRCA2, BRIP1, CHEK22, EPCAM3, MLH1, MSH2, MSH6, PALB2, PTEN, RAD51C, RAD51D, STK11, TP53|
|Hereditary Prostate Cancer||ATM1, BRCA1, BRCA2, CHEK22, EPCAM3, HOXB13, MLH1, MSH2, MSH6|
|Hereditary Colorectal Cancer (including Lynch syndrome) Panel||APC, BMPR1A, EPCAM3, MLH1, MSH2, MSH6, MUTYH, NTHL1, PMS24, POLD1, POLE, PTEN, SMAD4, STK11, TP53|
|Hereditary Melanoma Cancer Panel||BAP1, BRCA2, CDK4, CDKN2A, PTEN|
|Hereditary Pancreatic Cancer Panel||APC, BRCA1, BRCA2, CDKN2A EPCAM3, MLH1, MSH2, MSH6, PALB2, STK11, TP53, VHL|
Table 1. The genes included in each panel.
Target region for all genes includes full coverage of exons and exon/intron boundaries up to +/- 20bp
Panel does not cover promoter, 5’ or 3’ UTR
Interpretation is based on the MANE transcript
1Reporting is restricted to the truncating or frameshift variants only and c.7271T>G variants in ATM.
2Truncating or frameshift variants in CHEK2.
3Exon deletion of exon 8 to 9 of EPCAM.
4PMS2 and its pseudogene PMS2CL share high sequence homology for exons 12-15. This test does not distinguish whether variants seen in PMS2 originate from PMS2 or PMS2CL. Further testing may be required to disambiguate any variants found in exon 12-15 of PMS2.
Further information regarding these genes can be found here
A larger research panel incorporating 129 genes is available for research only use. Raw data and secondary analysis services are available.
How are samples taken?
Our hereditary cancer panels use genomic DNA (gDNA) extracted from saliva or blood samples.
For saliva samples, a complete sampling kit containing a sample collection tube and full instructions is available for self-sampling.
Click here for more information on sample requirements.
How are samples sequenced?
Our hereditary cancer testing service is delivered through our Next Generation Sequencing (NGS) pipeline. We use hybridisation library enrichment and Illumina sequencing to generate high-quality sequencing data. An in-house bioinformatics pipeline has been developed to detect single nucleotide variants (SNVs), indels and copy number variants (CNVs).
To ensure high confidence in the results, key performance parameters have been determined through extensive validation.
Sensitivity (ability of assay to detect true positive results) was assessed using 323 SNVs, 48 (1-28bp) deletions/insertions variants, and 20 CNVs. 100% sensitivity was observed across all variant types.
Based on sample size the 95% CI for sensitivity for SNVs is >98%, indels >92% and CNVs >83%. This is a measure of the confidence in the assay sensitivity and is based on the number of variants tested, therefore it is influenced by the availability of control samples, which for indels and CNVs is limited.
Specificity (ability of assay to detect true negative results) was assessed by comparing true negative nucleotides from the ‘Genome In A Bottle’ consensus sequence with data generated using our Hereditary cancer comprehensive panel. Specificity >99.99% was achieved.
Reproducibility was assessed across 6 repeat samples encompassing 80 variants. Results showed 100% reproducibility.
The laboratory offers an efficient and effective, quality-driven service which ensures the high performance of our hereditary cancer testing service. This is underpinned by a strong and robust Quality Management System.
Hereditary Cancer Panel Results
What do the results mean?
Detection of a pathogenic or likely pathogenic variant means that a variant has been found that increases the risk of the patient developing a certain cancer, but this does not mean that cancer will definitely occur. Genetic variants can occur naturally as we get older, and they are also influenced by both environmental and lifestyle factors.
Hereditary cancer susceptibility is linked to genes known as tumour suppressors. The body has two copies of these genes, and a single functional copy of the gene is sufficient at preventing cancer from developing; however, by having a pre-existing variant in a tumour suppressor gene, the risk of both copies being inactivated through a random second fault is increased. In essence, cancer has been given a head start and if the body is found to have these inherited genetic mutations, then a patient’s chances of developing certain types of cancers are higher compared to a person who does not have these genetic variations.
If no clinically relevant variant is detected, this means that we have not found any evidence of a genetic variant that is linked to cancer susceptibility. This lowers the risk of a genetic predisposition to cancer but does not exclude it. Variants can exist in genes not covered by the hereditary cancer panel, as well as in genomic regions that fall outside of the scope of testing, such as deep intronic variants or promoter regions.
Participation in national screening programmes remains important, as well as adopting a healthy lifestyle, as at least 90% of cancers are sporadic.
How do we Interpret genetic variants?
At Informed Genomics, genetic variants are interpreted using the following methods:
- Interpretation based on ACMG (American College of Medical Genetics), ACGS (Association for Clinical Genomics Science) and CanVar-UK (Cancer Predisposition Gene Variant Database) specifications.
- Using evidence-based criteria variants are described as pathogenic, likely pathogenic, variants of unknown significance, likely benign and benign.
- We standardise our interpretation utilising the latest clinical decision support software providing our HCPC registered scientists with the latest evidence and database resources for determining the pathogenicity of variants
What are variants of unknown significance (VUS)?
Variants of unknown significance are variants where there is either insufficient evidence to support whether they are pathogenic or benign, or the evidence is conflicting.
As these variants cannot be acted on, they are not reported. As our understanding is constantly evolving due to continued research in this field, VUS can change classification. However, if, over time, there is sufficient new evidence to support the reclassification of a VUS to pathogenic, a new report will be issued.
The report issued will contain all the actionable results from the hereditary cancer panel. If a genetic variant is found, the report will provide the impact, implications, and recommended actions which will be fully explained to patients via the genetic counselling process. Our genetic counsellor will also discuss health implications for patients and their families.
If no clinically significant variant is found, the report will clearly state this.
What is cancer?
Cancer is uncontrolled cell growth in an area of the body. When uncontrolled cell growth happens, it can form a tumour. Cancerous tumours can spread to other tissues which can affect how the body functions. Cancer is caused by variants in genes which normally control the growth and replication of cells. For more information please see Cancer Research UK.
What is hereditary cancer?
Can I get tested if I have cancer?
Yes. The test is available to all adults over the age of 18 regardless of any known health conditions and family history. Many people get tested when they have been diagnosed with cancer to find out if they have an inherited susceptibility gene which could have resulted in the cancer developing. This information can then be used to inform other family members.
Which hereditary cancers do you cover?
Informed Genomics offer a range of testing kits to study genes associated with the most common hereditary cancers ranging from a comprehensive multi-cancer testing kit to targeted kits for breast, ovarian, colorectal, prostate, melanoma and pancreatic cancer (panel in table 1).
Which genes are covered in the tests?
The genes covered in each hereditary cancer testing kit are included in the table 1. All genes have been expertly curated and have known clinical associations with increased cancer risk.
How were the genes selected?
The genes selected in the Informed Genomics hereditary cancer testing kits have been expertly chosen using scientific and medical literature and have been developed in accordance with national testing guidelines. All genetic variants reported will be clinically actionable and allow for informed decisions regarding risk management programmes.
Are the Ashkenazi Jewish common founder mutations associated with hereditary breast and ovarian cancer covered?
What is Next Generation Sequencing?
How are my results analysed and interpreted?
What will happen to my results?
What will happen to my sample after testing?
What happens if my tube breaks or I need a replacement tube?
Please contact the laboratory via firstname.lastname@example.org to request a repeat tube or for any further questions regarding sampling.
Where can I find out more information?
If you would like more information on any of our hereditary cancer testing kits or the testing process, please get in touch will us via email email@example.com
Contact us to find out more about our Hereditary Cancer Testing Service
Quinton Business Park