Invitae Multi-Cancer Panel

AIP, ALK, APC, ATM, AXIN2, BAP1, BARD1, BLM, BMPR1A, BRCA1, BRCA2, BRIP1, CASR, CDC73, CDH1, CDK4, CDKN1B, CDKN1C, CDKN2A, CEBPA, CHEK2, CTNNA1, DICER1, DDIS3L2, EGFR, EPCAM, FH, FLCN, GATA2, GPC3, GREM1, HOXB13, HRAS, KT, MAX, MEN1, MET, MITF, MLH1, MSH2, MSH3, MSH6, MUTYH, NBN, NF1, NF2, NTHL1, PALB2, PDGFR1A, PHOX2B, PMS2, POLD1, POLE, POT1, PRKAR1A, PTCH1, PTEN, RAD50, RAD51C, RAD51D, RB1, RECQL4, RET, RUNX1, SDHA, SHAF2, SDHB, SDHC, SDHD, SMAD4, SMARCA4, SMARCB1, SMARCE1, STK11, SUFU, TERC, TERT, TMEM127, TP53, TSC1, TSC2, VHL, WRN, WT1

A personalised results report will be sent to the customer and made available to their clinician (upon the customer’s consent).

There are three possible result outcomes from this test:

• A positive result – a pathogenic or likely pathogenic mutation has been detected
• A Variant of Unknown Significance (VUS) result
• A negative result – no pathogenic mutation detected

Positive: In cases where a patient has already been diagnosed with cancer, a positive result will mean that a fault in one or more in the patient’s genes has been found. Therefore, they have an increased risk of developing cancer as a second primary.

If taking the test to understand an individual’s risk of developing the cancer(s) tested for, a positive result will also mean that a fault in one or more of their genes has been found. Therefore, they have an increased risk of developing the cancer(s) tested for.

Negative: If the patient has already been diagnosed with cancer; a negative result will mean that the test has not identified any faults in the known genes. Therefore, they have no variants in the genes analysed that put them at high risk of developing cancer as a second primary.

However, if an individual is taking this test to understand their risk of developing the cancer tested for, a negative test result will mean that the test has not identified any faults in the known genes. Therefore, they have no variants in the genes analysed that put them at risk of developing the cancer(s) tested for.

Variant of Unknown Significance: The test result could show you have a Variant of Unknown Significance (VUS). This means that the test has identified a change in the sequence of one of your genes, but it is not yet known if that indicates a clinically significant cancer risk. However, it is unusual to receive a VUS result on any of these genes.

No personal medical guidance is provided with the test result. This should be obtained directly from the clinician.

Who can order this test from Everything Genetic? Healthcare providers and individuals.

Turnaround time: 2-3 weeks from receipt of sample in US laboratory.

Preferred specimen: Saliva and blood both accepted in either purple top EDTA blood collection tube or Oragene OG510 saliva collection tube.

Alternative specimen collection: gDNA also accepted.

Delivery information: Test kits will be sent out by using a Royal Mail Tracked service, unless otherwise arranged.

Pre and post-test clinical support is mandatory for those taking the test. This can either be provided by the clinician treating the patient or Everything Genetic’s Medical Director, Dr James Mackay.

This unique and personal clinical support service offered by Everything Genetic gives patients and their relatives the guidance and support they need so they understand their results and what they should do next.

Everything Genetic’s pre-test clinical support is provided through a clinically guided informational video which explains:

• What the test is for
• Why patients should take the test
• What it does and doesn’t test for
• What the possible results are from taking the test

If the results show a negative or VUS result, the patient will receive a clinically guided information video explaining what the results mean and what they should do next. A results report will also be sent to the patient and/or clinician via email, with the option of speaking to our Medical Director, Dr James Mackay.

If the results show a positive result, a private consultation will be arranged with either our Medical Director or the clinician who referred them. Following the consultation, a results report will be sent via email.

For clinicians who provide their own pre and post-test clinical support, the results will be sent directly to them.

Read more about our Medical Director, Dr James Mackay >>

The Invitae Multi-Cancer Panel analyses 84 genes associated with hereditary cancers across eight major organ systems. Individuals with a pathogenic variant in one of the genes on this panel have an increased risk of developing cancer, many of which may be difficult both to detect and to treat. Identifying those at elevated risk may guide implementation of additional screening, surveillance, and interventions. These efforts may result in risk-reduction and early diagnosis, increasing the chances of successful treatment and survival.

Breast cancer
The average woman’s lifetime risk of developing breast cancer is 12%. Pathogenic variants in BRCA1 and BRCA2 account for most cases in individuals with a strong family history or an early onset diagnosis. However, there are other genes associated with hereditary breast and ovarian cancer syndrome (HBOC).

Ovarian
The general population risk for ovarian cancer is 1.3%. Lynch syndrome and hereditary breast and ovarian cancer syndrome (HBOC) are due to pathogenic variants in the BRCA1 and BRCA2 genes and are the most common causes of inherited ovarian cancer. Ovarian cancer can also be caused by pathogenic variants in several other hereditary cancer genes.

Uterine
The general population risk for uterine cancer is 2.7%. Lynch syndrome is the most common inherited cause of uterine cancer, although there are other hereditary cancer genes associated with this cancer type.

Colorectal
Colorectal cancer (CRC) is the fourth-most-common cancer diagnosis in the UK. Hereditary colorectal cancer syndromes are generally divided into two types: Lynch syndrome and polyposis syndromes. Lynch syndrome, also called hereditary non-polyposis colon cancer (HNPCC), is caused by pathogenic variants in EPCAM, MLH1, MSH2, MSH6, and PMS2 and is the most common inherited cause of colorectal cancer. Polyposis syndromes are characterised by the development of numerous precancerous polyps, which may become malignant.

Gastric
Gastric cancer occurs in approximately 1 in 93 individuals in the general population. Gastric adenocarcinomas account for 90%–95% of gastric cancers and are further histologically divided into intestinal type and diffuse type. Pathogenic variants in CDH1 are the most common cause of hereditary gastric cancer; however, there are other genes associated with an increased risk of gastric tumours. Gastrointestinal stromal tumours (GISTs) are characterised as sarcomas and are rare tumours of the GI tract that account for 1%–3% of all gastric cancers. This panel includes genes that increase risk for each of these types of gastric tumours.

Pancreatic
There are two main types of pancreatic cancer: cancer of the exonic pancreas (pancreatic adenocarcinoma), which accounts for 95% of pancreatic tumours, and pancreatic neuroendocrine tumours. Hereditary pancreatic cancer can be caused by BRCA2 and CDKN2A, as well as by several other genes. This panel contains genes that are commonly associated with an increased risk for both types of pancreatic cancer.

Renal/urinary tract
The general population risk of developing kidney cancer is approximately 1.6%. The lifetime risk of developing bladder cancer is 1%–3.8%, with approximately 75,000 new cases diagnosed in the United States each year. Unlike sporadic cases, hereditary cancers of the kidneys and urinary tract are often characterised by earlier disease onset or multifocal or bilateral tumours. Hereditary urinary tract cancers may also be syndromic and associated with other non-urinary features.

Prostate
A man’s lifetime risk for developing prostate cancer is 1 in 7 (15%). Inherited pathogenic variants in certain genes—particularly ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PMS2, and TP53—account for some cases of hereditary prostate cancer. Men with pathogenic variants in these genes have an increased risk of developing prostate cancer and, in some cases, other cancers as well.

Melanoma
Most cases of melanoma skin cancer is isolated and sporadic. While the number of individuals who have an inherited risk of melanoma is unknown, it is thought to be low. An estimated 8% of individuals with melanoma also have a first-degree relative with the disease; approximately 1%–2% of people with melanoma have two or more affected close relatives. This panel includes genes associated with an increased risk for melanoma skin cancer.

Thyroid
Thyroid cancer occurs in approximately 13 per 100,000 individuals in the general population each year. The most common type of thyroid cancer, accounting for over 90% of all cases, is non-medullary thyroid cancer (NMTC). Approximately 3%–10% of NMTC cases have a familial component. Medullary thyroid carcinoma (MTC) is a relatively uncommon type of thyroid malignancy and is more strongly associated with hereditary cancer syndromes. The familial form of MTC accounts for 20%–25% of cases and is usually a component of multiple endocrine neoplasia type 2 (MEN2), including subtypes MEN2A and MEN2B, or presents as familial MTC (FMTC) syndrome.

Paraganglioma (PGL) and pheochromocytoma (PCC)
PGL are rare, adult-onset neuroendocrine tumours that may or may not be malignant. PGL can develop throughout the body, from the middle ear and skull base (called head and neck PGL, or HNP) to the adrenal glands (called pheochromocytomas (PCC)). Most cases are sporadic, but approximately one-third are familial. Familial PGL/PCC can be non-syndromic; however, it can also be a feature of an underlying condition such as neurofibromatosis type 1, von Hippel-Lindau syndrome, or multiple endocrine neoplasia type 2. This panel includes genes associated with hereditary PGL/PCC.

Brain and nervous system (including central nervous system (CNS) and peripheral nervous system (PNS)
The general population risk for developing a CNS tumour is 0.55%–0.69%. PNS tumours are rare in adults and children while CNS tumours are the most common cancers among children ages 0–19. Approximately 5% of CNS tumours are hereditary and due to a pathogenic variant (an identifiable change in a gene); the remainder are isolated and occur sporadically. Unlike sporadic cases, both hereditary CNS and PNS tumours may be syndromic and associated with extra-CNS features.

Sarcoma
A sarcoma is a rare type of cancer that develops from a variety of connective tissues, including bone, soft tissue, fat, muscle, nerves, fibrous tissues, blood vessels, and deep skin tissues. Sarcomas most often develop in the limbs but can be found in any part of the body. Most cases are sporadic and not inherited, but several known hereditary conditions are associated with an increased risk of sarcoma. Inherited pathogenic variants in certain genes, such as those included on this panel, account for some cases of hereditary sarcoma. Individuals with pathogenic variants in these genes have an increased risk of developing sarcomas and, in some cases, other cancers as well.

Myelodysplastic syndrome (MDS)/leukaemia
MDS and acute myeloid leukaemia (AML) generally occur in the elderly population and the incidence increases with age. Cases of early onset MDS/AML in children or young adults may be associated with underlying genetic predisposition syndromes. Hereditary MDS or AML may occur due to certain genetic syndromes that are typically associated with other distinctive, characteristic features. Isolated familial MDS/AML is characterised by a strong family history of MDS or AML without other apparent phenotypic features. Isolated familial occurrences appear to be rare but may be underdiagnosed. This panel includes genes that may increase risk for MDS and leukaemia.

Assay information

This test is developed by Invitae, a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory. The test performs analysis of clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons, depending on the specific gene or test. It also includes the analysis of select non-coding variants.

Sensitivity

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae’s methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced.

Validations and papers

View all validation documents and papers for this genetic test here >>