Identifying lung tumors that may respond to targeted therapies by simultaneously assessing multiple genes involved in rearrangements resulting in fusion transcripts
Diagnosing and managing patients with lung cancer
This test identifies specific gene fusions (rearrangements) involving the ALK, ROS1, and RET genes, MET exon 14 skipping, and expression imbalance for ALK, ROS1, RET, NTRK1, NTRK2, and NTRK3 genes.
Expression imbalance assays have the benefit that provide an indication of the presence of a fusion not covered by the specific fusion panel.
This test is performed to evaluate gene fusions (rearrangements) within solid tumor, in particular lung cancer, specimens.
This test evaluates formalin-fixed, paraffin-embedded tumor or cytology slides from patients with lung cancer for gene fusions (rearrangements) to identify candidates for targeted therapy.
Current data suggests that lung carcinomas with ALK, ROS1, RET rearrangements and MET exon 14 skipping may be sensitive to corresponding tyrosine kinase inhibitors.
Current data suggests that solid tumors with NTRK rearrangements may be sensitive to multikinase inhibitors.
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| SLIRV | Slide Review in MG | No | Yes |
When this test is ordered, slide review will always be performed at an additional charge.
Polymerase Chain Reaction (PCR)
ALK
Lung cancer fusion
Lung cancer rearrangement
MET exon 14
NTRK1
NTRK2
NTRK3
RET
ROS1
Mayo Complete
When this test is ordered, slide review will always be performed at an additional charge.
Varies
Multiple oncology (cancer) gene panels are available. For more information see Hematology, Oncology, and Hereditary Test Selection Guide.
Pathology report (final or preliminary) at minimum containing the following information must accompany specimen 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
This assay requires at least 10% tumor nuclei.
-Preferred amount of tumor area with sufficient percent tumor nuclei: tissue 36 mm(2)
-Minimum amount of tumor area: tissue 18 mm(2)
-These amounts are cumulative over up to 10 unstained slides and must have adequate percent tumor nuclei.
-Tissue fixation: 10% neutral buffered formalin, not decalcified
Preferred:
Specimen Type: Tissue block and cell block
Collection Instructions: Submit a formalin-fixed, paraffin-embedded tissue block or cell block with acceptable amount of tumor tissue.
Acceptable
Specimen Type: Tissue slides
Slides: 1 Stained and 5 unstained
Collection Instructions: Submit 1 slide stained with hematoxylin and eosin and 5 unstained, nonbaked slides wit 5-micron thick sections of the tumor tissue.
Note: The total amount of required tumor nuclei can be obtained by scraping up to 5 slides from the same block.
Additional Information: Unused unstained slides will not be returned.
Specimen Type: Cytology slides (direct smears)
Slides: 1 to 3 Slides for smears
Collection Instructions: Submit 1 to 3 slides unstained or stained with Diff Quik or Pap and coverslipped with a preferred total of 5000 nucleated cells or a minimum of at least 3000 nucleated cells.
Note: Glass coverslips are preferred; plastic coverslips are acceptable but will result in longer turnaround times.
Additional Information: Cytology slides used in testing will have everything scraped and not be returned.
See Specimen Required
| Specimens that have been decalcified (all methods) Specimens that have not been formalin fixed, paraffin-embedded, except for cytology slides Extracted nucleic acid (DNA or RNA) | Reject |
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Refrigerated | |||
Identifying lung tumors that may respond to targeted therapies by simultaneously assessing multiple genes involved in rearrangements resulting in fusion transcripts
Diagnosing and managing patients with lung cancer
This test identifies specific gene fusions (rearrangements) involving the ALK, ROS1, and RET genes, MET exon 14 skipping, and expression imbalance for ALK, ROS1, RET, NTRK1, NTRK2, and NTRK3 genes.
Expression imbalance assays have the benefit that provide an indication of the presence of a fusion not covered by the specific fusion panel.
This test is performed to evaluate gene fusions (rearrangements) within solid tumor, in particular lung cancer, specimens.
When this test is ordered, slide review will always be performed at an additional charge.
Targeted cancer therapies are defined as antibody or small molecule drugs that block the growth and spread of cancer by interfering with specific cell molecules involved in tumor growth and progression. Multiple targeted therapies have been approved by the US Food and Drug Administration for treatment of specific cancers. Molecular genetic profiling is often needed to identify targets amenable to targeted therapies and to minimize treatment costs and therapy-associated risks.
Fusions involving the NTRK1, NTRK2, or NTRK3 genes (ie, NTRK gene fusions) form through intra- and interchromosomal rearrangements. NTRK gene fusions lead to activation of downstream MAPK, PIK, and STAT3 signaling pathways and act as oncogenic drivers of multiple types of pediatric and adult solid tumors. In solid tumors, the presence of an NTRK gene fusion is a biomarker for response to tropomyosin receptor kinase inhibitor therapy.
Lung cancers harboring ALK rearrangements are resistant to epidermal growth factor receptor tyrosine kinase inhibitors but may be highly sensitive to ALK inhibitors, like Xalkori (crizotinib). The drug Xalkori works by blocking certain kinases, including those produced by the abnormal ALK gene. Clinical studies have demonstrated that Xalkori treatment of patients with tumors exhibiting ALK rearrangements can halt tumor progression or result in tumor regression.
RET rearrangements occur in approximately 2.5% to 10% of sporadic papillary thyroid cancer(1) and 1% to 3% of non-small cell lung cancer. The most prevalent fusions are KIF5B exon 15 - RET exon 12 and KIF5B exon 16 - RET exon 12, which represent over 75% of RET fusions.
ROS1 (c-ros oncogene 1), originally described in glioblastomas, has been identified as a potential relevant therapeutic target in lung adenocarcinoma. Crizotinib has shown in vitro activity and early evidence of clinical activity in ROS1-rearranged tumors.
Many cases of METex14 alterations are found in lung adenocarcinomas, these events have a much higher incidence in pulmonary sarcomatoid carcinomas. Approximately 20% to 30% of sarcomatoid carcinomas harbor METex14 alterations.
An interpretive report will be provided.
The interpretation of molecular biomarker analysis includes an overview of the results and the associated diagnostic, prognostic, and therapeutic implications.
This test cannot differentiate between somatic and germline alterations. Additional testing may be necessary to clarify the significance of results if there is a potential hereditary risk.
A negative result does not rule out the presence of a rearrangement (fusion) that may be present but below the limits of detection of this assay.
Gene fusions (rearrangements) and expression imbalance involving the ALK, ROS1, RET, NTRK1, NTRK2, and NTRK3 genes only will be detected. This test does not detect point mutations, deletion-insertion mutations, large single or multiexon deletions or duplications, or genomic copy number variants in any of the genes tested.
Rare alterations (ie, polymorphisms) may be present that could lead to false-negative or false-positive results.
The presence or absence of a variant may not be predictive of response to therapy in all patients.
Test results should be interpreted in the context of clinical findings, tumor sampling, and other laboratory data. If results obtained do not match other clinical or laboratory findings, contact the laboratory for updated interpretation. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.
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 polymerase chain reaction failure.
1. Vaishnavi A, Capelletti M, Le AT, et al: Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.Nat Med. 2013 Nov;19(11):1469-1472
2. US Food and Drug Administration (FDA): Table of Pharmacogenomic Biomarkers in Drug Labeling. FDA; Updated August 11, 2022, Accessed February 3, 2023. Available at www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling
3. Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Ahn MJ, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385-94. doi: 10.1056/NEJMoa1214886
4. Sehgal K, Patell R, Rangachari D, Costa DB. Targeting ROS1 rearrangements in non-small cell lung cancer with crizotinib and other kinase inhibitors. Transl Cancer Res. 2018;7(Suppl 7):S779-S86. doi: 10.21037/tcr.2018.08.11
5. Drilon A, Oxnard GR, Tan DSW, Loong HHF, Johnson M, Gainor J, et al. Efficacy of Selpercatinib in RET fusion-positive non-small-cell lung cancer. N Engl J Med. 2020;383(9):813-24. doi: 10.1056/NEJMoa2005653
6. Cocco E, Scaltriti M, Drilon A: NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018 Dec;15(12):731-747. doi: 10.1038/s41571-018-0113-0
7. Frampton GM, Ali SM, Rosenzweig M, Chmielecki J, Lu X, Bauer TM, et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov. 2015;5(8):850-9. doi: 10.1158/2159-8290.CD-15-0285
Qualitative detection using the Idylla GeneFusion Assay is performed to detect rearrangements (fusions) within the ALK, ROS1 and RET genes, MET exon 14 skipping, and expression imbalance for ALK, ROS1, RET, NTRK1, NTRK2 and NTRK3 genes. See Targeted Genes and Methodology Details for MayoComplete Lung Rearrangements for details regarding the targeted gene regions evaluated by this test.(Unpublished Mayo method)
A pathology review and macro dissection to enrich for tumor cells are performed prior to slide scraping.
Monday through Friday
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
81449
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| MCLNR | MayoComplete Lung Rearrangements | 73977-1 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 618280 | Result | 82939-0 |
| 618281 | Interpretation | 69047-9 |
| 618282 | Additional Information | 48767-8 |
| 618283 | Specimen | 31208-2 |
| 618284 | Tissue ID | 80398-1 |
| 618285 | Method | 85069-3 |
| 618286 | Disclaimer | 62364-5 |
| 618287 | Released By | 18771-6 |