The Invitae Multi-Cancer Panel analyzes 84 genes associated with hereditary cancers across major organ systems, including:
The Invitae Multi-Cancer Panel is designed to maximize diagnostic yield for individuals with a personal or family history of mixed cancers affecting multiple organ systems.
Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
PTEN: Deletion/duplication analysis covers the promoter region.
AIP ALK APC ATM AXIN2 BAP1 BARD1 BLM BMPR1A BRCA1 BRCA2 BRIP1 CASR CDC73 CDH1 CDK4 CDKN1B CDKN1C CDKN2A CEBPA CHEK2 CTNNA1 DICER1 DIS3L2 EGFR EPCAM FH FLCN GATA2 GPC3 GREM1 HOXB13 HRAS KIT MAX MEN1 MET MITF MLH1 MSH2 MSH3 MSH6 MUTYH NBN NF1 NF2 NTHL1 PALB2 PDGFRA PHOX2B PMS2 POLD1 POLE POT1 PRKAR1A PTCH1 PTEN RAD50 RAD51C RAD51D RB1 RECQL4 RET RUNX1 SDHA SDHAF2 SDHB SDHC SDHD SMAD4 SMARCA4 SMARCB1 SMARCE1 STK11 SUFU TERC TERT TMEM127 TP53 TSC1 TSC2 VHL WRN WT1
AIP ALK APC ATM AXIN2 BAP1 BARD1 BLM BMPR1A BRCA1 BRCA2 BRIP1 CASR CDC73 CDH1 CDK4 CDKN1B CDKN1C CDKN2A CEBPA CHEK2 CTNNA1 DICER1 DIS3L2 EGFR EPCAM FH FLCN GATA2 GPC3 GREM1 HOXB13 HRAS KIT MAX MEN1 MET MITF MLH1 MSH2 MSH3 MSH6 MUTYH NBN NF1 NF2 NTHL1 PALB2 PDGFRA PHOX2B PMS2 POLD1 POLE POT1 PRKAR1A PTCH1 PTEN RAD50 RAD51C RAD51D RB1 RECQL4 RET RUNX1 SDHA SDHAF2 SDHB SDHC SDHD SMAD4 SMARCA4 SMARCB1 SMARCE1 STK11 SUFU TERC TERT TMEM127 TP53 TSC1 TSC2 VHL WRN WT1
The Invitae Multi-Cancer Panel analyzes 84 genes associated with hereditary cancers across several 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%. Although there are a number of other genes associated with hereditary breast cancer, hereditary breast and ovarian cancer syndrome (HBOC) due to pathogenic variants in the BRCA1 and BRCA2 genes accounts for most cases in individuals with a strong family history or early onset diagnosis.
Ovarian
The general population risk for ovarian cancer is ~1.3%. Lynch syndrome and hereditary breast and ovarian cancer syndrome (HBOC) are the most common causes of ovarian cancer. In addition, there are other genes on this panel associated with hereditary predisposition to ovarian cancer.
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 a number of other hereditary cancer genes on this panel associated with this cancer type.
Colorectal
Colorectal cancer (CRC) is the third-most-common cancer diagnosis in the United States. 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 characterized by the development of numerous precancerous polyps, which may become malignant. This panel includes genes associated with both Lynch syndrome and polyposis.
Gastric
Gastric cancer occurs in ~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. One cause of hereditary gastric cancer is a pathogenic variant in CDH1, which causes hereditary diffuse gastric cancer syndrome. However, there are a number of other genes in which pathogenic variants increase the risk of gastric tumors. Gastrointestinal stromal tumors (GISTs) are characterized as sarcomas and are rare tumors 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 tumors.
Pancreatic
There are two main types of pancreatic cancer: cancer of the exonic pancreas (pancreatic adenocarcinoma), which accounts for 95% of pancreatic tumors, and pancreatic neuroendocrine tumors. Hereditary pancreatic cancer can be caused by BRCA2 and CDKN2A, as well as by several other genes. This panel includes genes that are most commonly associated with an increased risk for both types of hereditary pancreatic cancer.
Renal/urinary tract
The general population risk of developing kidney cancer is ~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. Most cases are sporadic and isolated, but approximately 5% of urinary tract cancers are hereditary. Unlike sporadic cases, hereditary cancers of the kidneys and urinary tract are often characterized by earlier disease onset and multifocal or bilateral tumors. Hereditary urinary tract cancers may also be syndromic and associated with other non-urinary features.
Prostate
Prostate cancer is the fifth-most-common malignancy in the world. A man’s lifetime risk for developing this type of cancer is ~1 in 7 (15%). While most cases of prostate cancer are sporadic and not inherited, approximately 5%–10% of cases are hereditary. This panel includes genes that increase risk for prostate cancer.
Melanoma
Most cases of melanoma are 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 melanoma and approximately 1%–2% of people with melanoma have two or more affected close relatives. This panel includes genes associated with a predisposition to melanoma.
Thyroid
Thyroid cancer occurs in ~13 per 100,000 individuals in the general population annually. 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. This panel includes genes associated with a predisposition to hereditary thyroid cancer.
Paraganglioma (PGL) and pheochromocytoma (PCC)
PGL are rare, adult-onset neuroendocrine tumors 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 and due to an identifiable pathogenic variant in a disease-causing gene. 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)
Pituitary adenoma (PA) is one of the most common types of intracranial tumors. Approximately 2% of all PA cases are attributable to FIPA (familial isolated pituitary adenoma) and the AIP gene accounts for ~20% of all FIPA cases. The general population risk for developing a CNS tumor is 0.55%–0.69%. PNS tumors are rare in adults and children; CNS tumors are the most common cancers among children ages 0–19. Approximately 5% of CNS tumors are hereditary and due to a pathogenic variant; the remainder are isolated and occur sporadically. Unlike sporadic cases, both hereditary CNS and PNS tumors may be syndromic and associated with extra-CNS features. This panel includes genes associated with hereditary predisposition to CNS and PNS tumors as well as a common cause of FIPA.
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 they can be found in any part of the body. Most cases of sarcoma are sporadic and not inherited, but several known genetic 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)/leukemia
MDS and acute myeloid leukemia (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 present as part of a particular genetic syndrome that also has additional prominent clinical features. Non-syndromic familial MDS/AML is characterized by a strong family history of MDS or AML without other apparent phenotypic features. Familial occurrences of MDS/AML appear to be rare, but they may be underdiagnosed. This panel includes genes that may increase risk for MDS and leukemia.
Individuals with a pathogenic variant identified by the Invitae Multi-Cancer Panel have an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develop cancer. Further, the same variant may manifest with different symptoms, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may be beneficial.
For gene-associated cancer risks:
The majority of genes on this panel have autosomal dominant inheritance for hereditary cancer predisposition. Several of these genes also have autosomal recessive inheritance, or result in clinically distinct autosomal recessive conditions. For detailed, gene-specific information, please see the individual gene pages.
This panel may be considered for individuals with:
There are also some common general features suggestive of a family with a hereditary cancer syndrome. These include:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers 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 in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
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. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
Gene | Transcript reference | Sequencing analysis | Deletion/Duplication analysis |
---|---|---|---|
AIP | NM_003977.3 | ||
ALK | NM_004304.4 | ||
APC* | NM_000038.5 | ||
ATM* | NM_000051.3 | ||
AXIN2 | NM_004655.3 | ||
BAP1 | NM_004656.3 | ||
BARD1 | NM_000465.3 | ||
BLM | NM_000057.3 | ||
BMPR1A* | NM_004329.2 | ||
BRCA1* | NM_007294.3 | ||
BRCA2* | NM_000059.3 | ||
BRIP1 | NM_032043.2 | ||
CASR | NM_000388.3 | ||
CDC73 | NM_024529.4 | ||
CDH1 | NM_004360.3 | ||
CDK4 | NM_000075.3 | ||
CDKN1B | NM_004064.4 | ||
CDKN1C | NM_000076.2 | ||
CDKN2A* | NM_058195.3; NM_000077.4 | ||
CEBPA | NM_004364.4 | ||
CHEK2 | NM_007194.3 | ||
CTNNA1 | NM_001903.3 | ||
DICER1* | NM_177438.2 | ||
DIS3L2 | NM_152383.4 | ||
EGFR | NM_005228.3 | ||
EPCAM* | NM_002354.2 | ||
FH* | NM_000143.3 | ||
FLCN | NM_144997.5 | ||
GATA2 | NM_032638.4 | ||
GPC3* | NM_004484.3 | ||
GREM1* | NM_013372.6 | ||
HOXB13 | NM_006361.5 | ||
HRAS | NM_005343.2 | ||
KIT | NM_000222.2 | ||
MAX* | NM_002382.4 | ||
MEN1* | NM_130799.2 | ||
MET* | NM_001127500.1 | ||
MITF* | NM_000248.3 | ||
MLH1* | NM_000249.3 | ||
MSH2* | NM_000251.2 | ||
MSH3* | NM_002439.4 | ||
MSH6* | NM_000179.2 | ||
MUTYH | NM_001128425.1 | ||
NBN | NM_002485.4 | ||
NF1* | NM_000267.3 | ||
NF2 | NM_000268.3 | ||
NTHL1 | NM_002528.6 | ||
PALB2 | NM_024675.3 | ||
PDGFRA | NM_006206.4 | ||
PHOX2B* | NM_003924.3 | ||
PMS2* | NM_000535.5 | ||
POLD1* | NM_002691.3 | ||
POLE | NM_006231.3 | ||
POT1 | NM_015450.2 | ||
PRKAR1A | NM_002734.4 | ||
PTCH1 | NM_000264.3 | ||
PTEN* | NM_000314.4 | ||
RAD50 | NM_005732.3 | ||
RAD51C | NM_058216.2 | ||
RAD51D | NM_002878.3 | ||
RB1* | NM_000321.2 | ||
RECQL4* | NM_004260.3 | ||
RET | NM_020975.4 | ||
RUNX1 | NM_001754.4 | ||
SDHA* | NM_004168.3 | ||
SDHAF2 | NM_017841.2 | ||
SDHB | NM_003000.2 | ||
SDHC* | NM_003001.3 | ||
SDHD | NM_003002.3 | ||
SMAD4 | NM_005359.5 | ||
SMARCA4 | NM_001128849.1 | ||
SMARCB1 | NM_003073.3 | ||
SMARCE1 | NM_003079.4 | ||
STK11 | NM_000455.4 | ||
SUFU | NM_016169.3 | ||
TERC | NR_001566.1 | ||
TERT | NM_198253.2 | ||
TMEM127 | NM_017849.3 | ||
TP53* | NM_000546.5 | ||
TSC1* | NM_000368.4 | ||
TSC2 | NM_000548.3 | ||
VHL | NM_000551.3 | ||
WRN* | NM_000553.4 | ||
WT1 | NM_024426.4 |
APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis. Sequencing analysis for exon 5 is limited to cds +/-10 bp.
ATM: Sequencing analysis for exons 6, 24, 43 includes only cds +/- 10 bp.
BMPR1A: Deletion/duplication analysis covers the promoter region.
BRCA1: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
BRCA2: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
CDKN2A (p14ARF): Analysis supports interpretation of the p14 and p16 proteins.
DICER1: Sequencing analysis for exons 22 includes only cds +/- 10 bp.
EPCAM: Sequencing analysis is not offered for this gene.
FH: Sequencing analysis for exon 9 is limited to cds +/-10 bp.
GPC3: Sequencing analysis for exon 3 is limited to cds +/-10 bp.
GREM1: Promoter region duplication testing only.
MAX: Sequencing analysis for exons 2 includes only cds +/- 10 bp.
MEN1: Sequencing analysis for exon 2 is limited to cds +/-10 bp.
MET: Sequencing analysis for exons 12 includes only cds +/- 10 bp.
MITF: c.952G>A, p.Glu318Lys variant only.
MLH1: Deletion/duplication analysis covers the promoter region. Sequencing analysis for exon 12 is limited to cds +/-10 bp.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation). Sequencing analysis for exons 2, 5 includes only cds +/- 10 bp.
MSH3: Sequencing analysis of the repeat region of exon 1 (5:79950697-79950765) is not offered
MSH6: Sequencing analysis for exons 7, 10 includes only cds +/- 10 bp.
NF1: Sequencing analysis for exons 2, 7, 25, 41, 48 includes only cds +/- 10 bp.
PHOX2B: Alanine repeat numbers for the commonly-expanded region in exon 3 are not determined.
PMS2: Sequencing analysis for exons 7 includes only cds +/- 10 bp.
POLD1: Sequencing analysis for exons 22 includes only cds +/- 10 bp.
PTEN: Deletion/duplication analysis covers the promoter region. Sequencing analysis for exons 8 includes only cds +/- 10 bp.
RB1: Sequencing analysis for exons 15-16 includes only cds +/- 10 bp.
RECQL4: Sequencing analysis for exons 13-14 is limited to cds +/-10 bp.
SDHA: Deletion/duplication analysis is not offered for this gene and sequencing analysis is not offered for exon 14. Sequencing analysis for exons 6-8 includes only cds +/- 10 bp.
SDHC: Sequencing analysis for exons 2, 6 includes only cds +/- 10 bp.
TP53: Deletion/duplication analysis covers the promoter region.
TSC1: Sequencing analysis for exons 21 includes only cds +/- 10 bp.
WRN: Deletion/duplication analysis is not offered for exons 10-11. Sequencing analysis for exons 8, 10-11 includes only cds +/- 10 bp.