FGFR Mutation Analysis, Urothelial Cancer

CPT: 81401; 81403; 88381
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Test Details

Synonyms

  • FGFR

Use

The therascreen FGFR RGQ RT-PCR Kit is a real-time, reverse transcription PCR test for the qualitative detection of two point mutations in exon 7 [p.R248C (c.742C>T), p.S249C (c.746C>G)], two point mutations in exon 10 [p.G370C(c.1108G>T) and p.Y373C (c.1118A>G)] and two fusions (FGFR3:TACC3v1, FGFR3:TACC3v3) in the fibroblast growth factor receptor 3 (FGFR3) gene in RNA samples derived from formalin-fixed paraffin-embedded (FFPE) urothelial tumor tissue. The test is indicated for use as an aid in identifying patients with urothelial cancer (UC) which harbor these alterations and are therefore eligible for treatment with Balversa(TM) (erdafitinib).

Specimens are processed using the RNeasy DSP FFPE Kit for manual sample preparation followed by reverse transcription and then automated amplification and detection on the Rotor-Gene Q MDx (US) instrument.

Table 1. therascreen FGFR RGQ RT-PCR Kit assays targets: Point mutations

Gene

Amino acid

CDS mutation

Cosmic ID

Exons

FGFR3

p.R248C

c.742C>T

COSM714

7

FGFR3

p.G370C

c.1108G>T

COSM716

10

FGFR3

p.S249C

c.746C>G

COSM715

7

FGFR3

p.Y373C

c.1118A>G

COSM718

10

Table 2. therascreen FGFR RGQ RT-PCR Kit assay targets: Fusions

Fusion ID

Genes involved

Genomic breakpoints

Exons

FGFR3:TACC3v1

FGFR3

[chr4:1808661]C

17

TACC3

G[chr4:1741428]

11

FGFR3:TACC3v3

FGFR3

[chr4:1808661]C

17

TACC3

G[chr4:1739324]

10

Limitations

Results from the product must be interpreted within the context of all relevant clinical and laboratory findings and are not to be used alone for diagnosis

The therascreen FGFR RGQ RT-PCR Kit is only to be used to test RNA derived from specimens of FFPE urothelial cancer tumors.

The therascreen FGFR RGQ RT-PCR Kit is only to be used to test RNA prepared using the RNeasy DSP FFPE Kit (Cat. No. 73604).

The therascreen FGFR RGQ RT-PCR kit is also designed to identify FGFR2 fusions FGFR2:BICC1 and FGFR2:CASP7 and FGFR3 fusion FGFR3:BAIAP2L1, because patients harboring these FGFR fusions were eligible for the clinical trial. However, the test is not clinically validated to detect these three fusions. Drug safety and efficacy has not been established for cases of UC harboring these fusions and no claims are made for the use of the therascreen FGFR RGQ RT-PCR kit as an aid in the selection of such patients for treatment with BALVERSA (erdafitinib).

Samples with results reported as "No FGFR Alteration Detected" may harbor FGFR alterations that are not detected by the therascreen FGFR RGQ RT-PCR Kit.

Detection of FGFR alterations is dependent on sample integrity and the amount of amplifiable cDNA which can be derived from the sample.

The therascreen FGFR RGQ RT-PCR Kit does not demonstrate any detectable cross-reactivity (resulting in a report of "Alteration Detected") between the FGFR gene alteration assays it includes.

The therascreen FGFR RGQ RT-PCR Kit provides a qualitative test result, generating either a positive or negative result call for each FGFR alteration.

The therascreen FGFR RGQ RT-PCR Kit uses a two-step RT-PCR procedure. As with all similar procedures, samples may become contaminated by external sources within the test environment, or potentially by the positive control. Test operators must exercise due caution to avoid contamination of samples and kit reagents.

Methodology

Specimens are processed using the RNeasy DSP FFPE Kit for manual sample preparation followed by reverse transcription and then automated amplification and detection on the Rotor-Gene Q MDx (US) instrument.

Specimen Requirements

Specimen

Formalin-fixed, paraffin-embedded tissue (FFPE) block or slides from tissue resection

Volume

Formalin-fixed, paraffin-embedded (FFPE) tissue block or 6 unstained slides at 4-5 µm with one matching H&E-stained slide or 7 unstained slides.

Minimum Volume

3 unstained slides at 4-5 µm and one matching H&E-stained slide or 4 unstained slides. Assay requires a minimum of >10% tumor cellularity and >100 mm2 total tumor area with <20% necrosis available for extraction. Minimum volume allows for one attempt at nucleic acid extraction.

Container

FFPE block or slides

Collection

Ship specimen at room temperature. Please direct any questions regarding this test to customer service at 800-345-4363.

Storage Instructions

Maintain blocks/slides at room temperature.

Causes for Rejection

• Specimen does not meet all of the above criteria for sample type, container, minimum volume, collection and storage.

• Specimens containing suspicious foreign material.

• No tumor tissue in FFPE block or slides.

• Broken or stained slides.

• Fixative other than formalin.

Clinical Information

Special Instructions

Please provide a copy of the pathology report. Testing will be delayed if the pathology report is not received. Please direct any questions regarding this test to customer service at 800-345-4363.

References

BALVERSA (Erdafitinib) US Prescribing Information.
Holland PM, Abramson RD, Watson R, Gelfand DH. Detection of specific polymerase chain reaction product by utilizing the 5'-3' exonuclease activity of Thermus aquaticus DNA polymerase. Proc Natl Acad Sci USA. 1991 Aug 15;88(16):7276-7280.1871133
Knowles MA, Hurst CD. Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat Rev Cancer. 2015 Jan;15(1):25-41.25533674
Ornitz DM, Itoh N. The Fibroblast Growth Factor signaling pathway. Wiley Interdiscip Rev Dev Biol. 2015 May-Jun;4(3):215-66.25772309
Rodriguez-Vida A, Saggese M, Hughes S, et al. (2015) Complexity of FGFR signaling in metastatic urothelial cancer. J Hematol Oncol. 2015 Oct 24;8:119.26497743

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