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  • Test code: 01361
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
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Invitae Renal/Urinary Tract Cancers Panel

Test description

The Invitae Renal/Urinary Tract Cancers Panel analyzes genes associated with an increased lifetime risk of developing cancers of the urinary tract (kidneys, renal pelvis, ureters, bladder and urethra). These genes were selected based on the available evidence to date to provide Invitae’s most comprehensive panel for hereditary renal/urinary tract cancers. Many of these genes are also associated with an increased risk of other cancer types.

The primary panel includes 24 genes associated with an increased lifetime risk of developing cancers of the urinary tract (kidneys, renal pelvis, ureters, bladder, and urethra). In addition to the primary panel, clinicians can also choose to include 8 genes that have preliminary evidence of an association with these cancer types. At this time, the association of these genes with renal/urinary tract cancers remain uncertain; however, some clinicians may wish to include genes that may prove to be clinically significant in the future. These genes can be added at no additional charge.

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.

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Primary panel (24 genes)

BAP1 CDC73 CDKN1C DICER1 DIS3L2 EPCAM FH FLCN GPC3 MET MLH1 MSH2 MSH6 PMS2 PTEN SDHB SDHC SMARCA4 SMARCB1 TP53 TSC1 TSC2 VHL WT1

Add-on Preliminary-evidence Genes for Renal/Urinary Tract Cancers (8 genes)

Genes with preliminary evidence of association with renal/urinary tract cancers are available to add on to the primary panel. Adding on preliminary-evidence genes can increase the number of variants of uncertain significance that are identified. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

BUB1B CEP57 CTR9 MITF PALB2 REST SDHA SDHD

  • Birt-Hogg-Dubé syndrome (BHD)
  • Lynch syndrome
  • Cowden syndrome
  • Li-Fraumeni syndrome (LFS)
  • Tuberous sclerosis complex (TSC)
  • Von Hippel-Lindau syndrome (VHL)
  • WT1-related Wilms tumor
  • Hereditary papillary renal cell carcinoma (HPRCC)
  • Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)
  • DICER1 syndrome
  • Perlman syndrome
  • Simpson-Golabi-Behmel syndrome
  • Rhabdoid tumor predisposition syndrome (RTPS)

Most cancers of the renal pelvis, ureter, urethra and bladder are transitional cell carcinomas while most renal cancers are adenocarcinomas; however, not all urinary tract tumors are malignant. The choice of treatment depends on many factors such as tumor size, number of tumors, if they are bilateral, and whether or not they are causing symptoms.

The general population risk of developing kidney cancer is approximately 1.6%. The lifetime risk of developing bladder cancer is from 1%–3.8%, and approximately 75,000 new cases are diagnosed annually in the United States. While most cases are sporadic and isolated, approximately 5% of urinary tract cancers are due to a heritable pathogenic variant. Unlike sporadic cases, hereditary renal and other urinary tract cancers are often characterized by earlier disease onset and multifocal or bilateral tumors. Further, hereditary urinary tract cancers may also be syndromic and associated with other non-urinary features.

Individuals with a pathogenic variant in one of these genes 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 can present differently, 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, see the table below.

GeneConditionRenal cancer riskUrinary tract cancer risk
BAP1 BAP1 hereditary cancer predisposition syndrome 10% (PMID: 26096145)
CDC73 CDC73-related disorders elevated (PMID: 15579037, 7912571)
CDKN1C Beckwith-Wiedemann syndrome up to 8% (Wilms) (PMID: 12138139)
DICER1 DICER1 syndrome elevated (PMID: 24481001, 21036787)
DIS3L2 Perlman syndrome elevated (PMID: 23613427)
EPCAM Lynch syndrome elevated (PMID: 20591884)
FH Hereditary leiomyomatosis and renal cell carcinoma 10%-16% (PMID: 12772087, 15724016)
FLCN Birt-Hogg-Dube syndrome 16% (PMID: 22146830)
GPC3 Simpson-Golabi-Behmel syndrome elevated (PMID: 2523897, 16398453)
MET Hereditary papillary renal cell carcinoma elevated (PMID: 24710684, 26052049)
MLH1 Lynch syndrome elevated (PMID: 20591884)
MSH2 Lynch syndrome elevated (PMID: 20591884)
MSH6 Lynch syndrome elevated (PMID: 20591884)
PMS2 Lynch syndrome elevated (PMID: 20591884)
PTEN Cowden and Cowden-like syndrome elevated (PMID: 22252256)
SDHB Hereditary paraganglioma-pheochromocytoma syndrome, Carney-Stratakis syndrome elevated (PMID: 18728283, 23083876)
SDHC Hereditary paraganglioma-pheochromocytoma syndrome, Carney-Stratakis syndrome elevated (PMID: 23083876)
SMARCA4 unknown (PMID: 25494491)
SMARCB1 Rhabdoid tumor predisposition syndrome type 1 elevated (PMID: 25494491)
TP53 Li-Fraumeni syndrome elevated (PMID: 2363254, 11219776) elevated (PMID: 20522432)
TSC1 Tuberous sclerosis complex 2%–5% (PMID: 21182496)
TSC2 Tuberous sclerosis complex 2%–5% (PMID: 21182496)
VHL von Hippel-Lindau syndrome 24%–45% (PMID: 26279462, 20833335, 21955200)
WT1 WT1-related conditions elevated (non-syndromic Wilms tumor) (PMID: 12193442, 25688735)

Elevated: There is evidence of association, but the penetrance and risk are not well characterized.
Unknown: Based on small studies, the risk may possibly be increased, but it is not well described.

Most of the genes on this panel have autosomal dominant inheritance in association with renal/urinary tract cancers. Some genes have other inheritance patterns and may result in clinically distinct conditions:

  • The GPC3 gene has X-linked inheritance.
  • MLH1, MSH2, PMS2 and MSH6 are associated with autosomal recessive constitutional mismatch repair deficiency (CMMR-D).
  • FH is associated with autosomal recessive fumarate hydratase deficiency.
  • SDHB is associated with autosomal recessive mitochondrial complex II deficiency.
  • DIS3L2 is associated with autosomal recessive Perlman syndrome.
  • VHL is associated with autosomal recessive familial erythrocytosis, type 2.

This panel may be considered for individuals whose clinical and family histories are suggestive of a hereditary urinary tract cancer syndrome, including:

  • early onset renal/urinary tract cancer (diagnosed ≤50)
  • multiple primary cancers in one person, one of which is a cancer of the kidney/urinary tract
  • two or more family members with renal/urinary tract cancer

There are also some common, general features suggestive of a hereditary cancer syndrome family. These include:
  • cancer diagnosed at an unusually young age
  • different types of cancer that have occurred independently in the same person
  • cancer that has developed in both organs of a set of paired organs (e.g., both kidneys)
  • several close blood relatives that have the same type of cancer
  • unusual cases of a specific cancer type (e.g., breast cancer in a man)

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Assay and technical information

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, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

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
BAP1 NM_004656.3
BUB1B NM_001211.5
CDC73 NM_024529.4
CDKN1C NM_000076.2
CEP57 NM_014679.4
CTR9 NM_014633.4
DICER1 NM_177438.2
DIS3L2 NM_152383.4
EPCAM* NM_002354.2
FH NM_000143.3
FLCN NM_144997.5
GPC3 NM_004484.3
MET NM_001127500.1
MITF* NM_000248.3
MLH1* NM_000249.3
MSH2* NM_000251.2
MSH6 NM_000179.2
PALB2 NM_024675.3
PMS2 NM_000535.5
PTEN* NM_000314.4
REST NM_005612.4
SDHA* NM_004168.3
SDHB NM_003000.2
SDHC NM_003001.3
SDHD NM_003002.3
SMARCA4 NM_001128849.1
SMARCB1 NM_003073.3
TP53* NM_000546.5
TSC1 NM_000368.4
TSC2 NM_000548.3
VHL NM_000551.3
WT1 NM_024426.4

EPCAM: Analysis is limited to deletion/duplication analysis.
MITF: Analysis is limited to the NM_000248.3:c.952G>A p.Glu318Lys variant.
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
PTEN: Deletion/duplication analysis covers the promoter region.
SDHA: Analysis is limited to sequencing analysis. No clinically-relevant del/dups have been reported.
TP53: Deletion/duplication analysis covers the promoter region.