Test Catalog

Test Id : TFGFR

FGFR Mutation and Fusion Analysis, Tumor

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identification of urothelial tumors that may respond to FGFR-targeted therapies

 

This test is not intended for use for hematological malignancies and does not assess germline alterations within the genes listed.

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test is an FDA-approved assay for the evaluation of somatic mutations and fusions in the FGFR3 and FGFR2 genes to identify urothelial carcinoma patients that may be eligible for treatment with FGFR-targeted therapies such as Balversa (erdafitinib).

 

This test uses targeted reverse transcriptase (RT)-PCR to evaluate for somatic mutations within the FGFR3 gene: R248C, S249C, G370C, and Y373C. RT-PCR is also used to identify certain rearrangements (fusions): FGFR3-TACC3v3 and FGFR3-TACC3v1. Furthermore, this test can identify fusions: FGFR3-BAIAP2L1, FGFR2-BICC1, and FGFR2-CASP7, however detection of these fusions is considered off-label use of the test. For more information see Clinical Information.

 

Of note, this test is performed to evaluate for somatic mutations and rearrangements (fusions) within solid tumor samples. This test is not intended for use for hematological malignancies. Additionally, this test does not assess for germline alterations within the genes listed.

Additional Tests
Lists tests that are always performed, at an additional charge, with the initial tests.

Test Id Reporting Name Available Separately Always Performed
SLIRV Slide Review in MG No Yes

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, slide review will always be performed at an additional charge.

Method Name
A short description of the method used to perform the test

Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

FGFR Mutation/Fusion Analysis Tumor

Aliases
Lists additional common names for a test, as an aid in searching

Fibroblast growth factor receptor

FGFR Mutation

FGFR Fusion

FGFR Companion Diagnostics

Urothelial cancer

Urothelial tumor

Urothelial

Bladder cancer

Bladder tumor

Bladder

Reverse transcriptase polymerase chain reaction

RT PCR

RT-PCR

FGFR3

FGFR2

R248C

S249C

G370C

Y373C

FGFR3-TACC3v1

FGFR3-TACC3v3

FGFR3-BAIAP2L1

FGFR2-BICC1

FGFR2-CASP7

FGFR

Therascreen

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, slide review will always be performed at an additional charge.

Specimen Type
Describes the specimen type validated for testing

Varies

Necessary Information

Pathology report (final or preliminary) at minimum containing the following information must accompany specimen in order for testing to be performed:

1. Patient name

2. Block number-must be on all blocks, slides and paperwork (can be handwritten on the paperwork)

3. Tissue collection date

4. Source of the tissue

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

This assay requires at least 10% tumor nuclei.

The amount of tissue needed is dependent on a variety of preanalytical factors (eg, cellularity, ischemic time, fixation).

The FFPE input required is equivalent to a 4–5 micron slide thickness with a total tumor surface area between 100 mm(2) and 500 mm(2) (inclusive). This can be created by combining material from multiple slides from one tissue block.

 

Preferred:

Specimen Type: Tissue block

Collection Instructions: Submit a formalin-fixed, paraffin-embedded tissue block.

 

Acceptable:

Specimen Type: Tissue slide

Slides: 1 stained and 10 unstained

Collection Instructions: Submit 1 slide stained with hematoxylin and eosin and 10 unstained, nonbaked slides with 5-micron thick sections of the tumor tissue.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Specimens that have been decalcified (all methods); specimens that have not been formalin-fixed, paraffin-embedded Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
Frozen
Refrigerated

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identification of urothelial tumors that may respond to FGFR-targeted therapies

 

This test is not intended for use for hematological malignancies and does not assess germline alterations within the genes listed.

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test is an FDA-approved assay for the evaluation of somatic mutations and fusions in the FGFR3 and FGFR2 genes to identify urothelial carcinoma patients that may be eligible for treatment with FGFR-targeted therapies such as Balversa (erdafitinib).

 

This test uses targeted reverse transcriptase (RT)-PCR to evaluate for somatic mutations within the FGFR3 gene: R248C, S249C, G370C, and Y373C. RT-PCR is also used to identify certain rearrangements (fusions): FGFR3-TACC3v3 and FGFR3-TACC3v1. Furthermore, this test can identify fusions: FGFR3-BAIAP2L1, FGFR2-BICC1, and FGFR2-CASP7, however detection of these fusions is considered off-label use of the test. For more information see Clinical Information.

 

Of note, this test is performed to evaluate for somatic mutations and rearrangements (fusions) within solid tumor samples. This test is not intended for use for hematological malignancies. Additionally, this test does not assess for germline alterations within the genes listed.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, slide review will always be performed at an additional charge.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

As high as 32% of individuals with urothelial cancer have been observed to have an activating fibroblast growth factor receptor (FGFR) alteration and approximately half of those are in FGFR3. The FGFR isotypes are part of the RAS/MAPK, PI3KAKT, PLCgamma, and STAT intracellular signaling pathways involved in cell proliferation and survival. FGFR mutations, primarily those occurring in the kinase domain, result in constitutive activation and contribute to tumorigenesis. The FGFR kinase inhibitor erdafitinib (BALVERSA) is a drug therapy approved by the FDA for individuals with FGFR3 and FGFR2-mutated advanced or metastatic urothelial carcinoma after platinum-containing chemotherapy has become ineffective.

 

Current data suggest that the efficacy of FGFR-targeted therapy in urothelial cancer is highest in patients with tumors demonstrating the presence of the FGFR3-activating mutations R248C, S249C, G370C, Y373C, and fusions FGFR3-TACC3v3, FGFR3-TACC3v1. As a result, the mutation status of FGFR is a critical marker for selecting patients for FGFR-targeted therapy.

 

This FDA approved test uses RNA extracted from the tumor tissue to evaluate for the presence of mutations of R248C, S249C, G370C, and Y373C in the FGFR3 gene, as well as fusions FGFR3-TACC3v3 and FGFR3-TACC3v1. A positive result showing any of these alterations indicates the presence of an FGFR mutation and may be useful for guiding the treatment of individuals with urothelial cancer.

 

This test was also designed to find fusions FGFR3-BAIAP2L1, FGFR2-BICC1, and FGFR2-CASP7. However, FDA approval of this assay to detect these fusions was not gained due to lack of patient samples. Drug efficacy and safety has not been established for these fusions, which were included in clinical trials. These fusions will be reported if detected but are considered off-label use of the test.

 

At this time, this test is approved specifically for patients with urothelial cancer. The utilization of this test in patients with other tumor types could be considered an off-label use of this test.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A negative (wild-type) result does not rule out the presence of a mutation or rearrangement (fusion) that may be present but below the limits of detection of this assay. It also does not rule out the presence of other activating mutations in the fibroblast growth factor receptor (FGFR) gene outside those that the assay was designed to detect.

 

The predictive value of FGFR testing applies to FGFR- kinase inhibitors therapy erdafitinib (BALSERVA), not to other therapeutic agents.

 

Not all patients who have FGFR mutations respond to FGFR-targeted therapies.

 

Rare polymorphisms exist that could lead to false-negative or false-positive results.

 

Reliable results are dependent on adequate specimen collection and processing. This test has been validated on cytology slides and formalin-fixed, paraffin-embedded tissues; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause PCR failure.

 

Test results should be interpreted in context of clinical findings, tumor sampling, and other laboratory data. If results obtained do not match other clinical or laboratory findings, please contact the laboratory for possible interpretation. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Helsten T, Elkin S, Arthur E, et al: The FGFR Landscape in Cancer: Analysis of 4,853 Tumors by Next-Generation Sequencing. Clin Cancer Res. 2016 Jan 1;22(1):259-267

2. Porebska N, Latko M, Kucinska M, et al: Targeting Cellular Trafficking of Fibroblast Growth Factor Receptors as a Strategy for Selective Cancer Treatment. J Clin Med. 2018 Dec 20;8(1). pii: E7

3. Bakkar AA, Wallerand H, Radvanyi F, et al: FGFR3 and TP53 gene mutations define two distinct pathways in urothelial cell carcinoma of the bladder. Cancer Res. 2003 Dec 1;63(23):8108-8112

Method Description
Describes how the test is performed and provides a method-specific reference

A PCR-based assay employing real-time PCR and allele-specific PCR technologies is used to test for 4 mutations within FGFR3 (R248C, S249C, G370C and Y373C) and 2 fusions (FGFR3-TACC3v1, FGFR3-TACC3v3). Although not FDA-approved, per package insert, this test may also detect 3 additional fusions in FGFR3 and FGFR2 (FGFR3-BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7.(Package insert: therascreen FGFR RGQ PCR Kit. Qiagen, 04/2019)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

5 to 7 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Unused portions of blocks will be returned. Unused slides: Indefinitely

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

0154U

Slide Review

88381

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports