Fibroblast growth factor receptors (FGFR) are tyrosine kinases involved in the transduction of growth factor signaling. Mutations and translocations affecting the genes that encode these proteins (primarily FGFR2 and FGFR3) occur in approximately 20% of urothelial carcinomas, as well as in many other types of cancer. These mutations and translocations result in constitutive activation of the receptor and downstream growth signaling. Amplification of FGFR genes is also well-described in urothelial carcinoma.
The detection of these mutations and translocations can have important treatment implications. Erdafitinib (Balversa) is an FGFR-inhibitor that is FDA-approved for the treatment of metastatic urothelial cancers harboring susceptible mutations or translocations involving FGFR2 or FGFR3. Other FGFR-targeted therapies are being investigated in clinical trials for the treatment of urothelial carcinoma and other cancers with FGFR alterations.
This DNA and RNA based test is performed by targeted next-generation sequencing and will detect mutations within the sequenced regions of FGFR2 (NM_000141.4; exons 7, 8, 9, 12 and 14) and FGFR3 (NM_000142.4; exons 7, 9, 14 and 16). Commonly mutated codons within FGFR3 that are covered by this assay include R248, S249, G370 and Y373. In addition, this test will detect activating FGFR2 and FGFR3 gene fusions including FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1 and FGFR2-CASP7. A complete list of sequenced regions and detectable fusion transcripts is available below.
Interpretive report provided.
This test will only detect mutations within specific gene regions and specific gene fusions (see University of Michigan Pathology Handbook for specific information). This test may fail to detect molecular alterations below the limit of detection of this assay (approximately 5%). Discordant results may rarely be observed between metastatic and primary tumors. This test cannot definitively distinguish between somatic and germline variants. Additional testing may be required if there is concern for a clinically relevant germline alteration. The clinical implications of the findings in this report may change based on evolution of the scientific literature.
For formalin-fixed, paraffin-embedded tissue, a block containing an area with a high percentage of neoplastic cells (for micro-/macro-dissection) is preferred. Unstained, UNBAKED slides (5-8, 10-micron slides; 10-15 if few neoplastic cells are present) with associated H&E stained slide are also acceptable. Decalcified tissue or other fixatives will be accepted and the assay attempted, however these may result in failed testing due to degraded nucleic acid. Both blocks and slides should be stored at room temperature. A Diff-Quik or Papanicolaou stained aspirate smear (preferable containing a high percentage and overall amount of neoplastic cells) is also acceptable. Store at room temperature.
By ordering this test the clinician acknowledges that informed consent has been obtained from the patient as required by applicable state or federal laws and the ordering clinician has authorization from the patient permitting MLabs to report the test results to the ordering clinician. Test includes microdissection billed as a separate additional charge. Test includes pathologist interpretation of results billed as a separate additional charge. This test is not available without interpretation.