Test Id : MCLNR
MayoComplete Lung Rearrangements, Rapid Test, Tumor
Useful For
Suggests clinical disorders or settings where the test may be helpful
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
Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request
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.
Highlights
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.
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
Polymerase Chain Reaction (PCR)
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
ALK
Lung cancer fusion
Lung cancer rearrangement
MET exon 14
NTRK1
NTRK2
NTRK3
RET
ROS1
Mayo Complete
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
Ordering Guidance
Multiple oncology (cancer) gene panels are available. For more information see Hematology, Oncology, and Hereditary Test Selection Guide.
Necessary Information
A 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
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.
-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: Submit 3, if available, or 2 of the following specimens.
Acceptable: Submit at least one of the following specimens.
Specimen Type: Tissue block
Collection Instructions: Submit a formalin-fixed, paraffin-embedded tissue block with acceptable amount of tumor tissue.
Specimen Type: Tissue slide
Slides: 1 Hematoxylin and eosin-stained and 10 unstained
Collection Instructions:
Submit the followings slides:
1 Slide stained with hematoxylin and eosin
AND
10 Unstained, nonbaked slides with 5-micron thick sections of the tumor tissue.
Note: The total amount of required tumor nuclei can be obtained by scraping up to 10 slides from the same block.
Additional Information: Unused unstained slides will not be returned.
Specimen Type: Cytology slide (direct smears or ThinPrep)
Slides: 1 to 3 Slides
Collection Instructions: Submit 1 to 3 slides stained and coverslipped with a total of 5000 nucleated cells (preferred) or at least 3000 nucleated cells (minimum).
Note: Glass coverslips are preferred; plastic coverslips are acceptable but will result in longer turnaround times.
Additional Information: Cytology slides will not be returned. An image of the slides will be stored per regulatory requirements.
Special Instructions
Library of PDFs including pertinent information and forms related to the test
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
See Specimen Required
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
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) | ||
| Refrigerated | |||
Useful For
Suggests clinical disorders or settings where the test may be helpful
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
Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request
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.
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
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.
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
The interpretation of molecular biomarker analysis includes an overview of the results and the associated diagnostic, prognostic, and therapeutic implications.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Vaishnavi A, Capelletti M, Le AT, et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.Nat Med. 2013;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;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
Method Description
Describes how the test is performed and provides a method-specific reference
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.
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
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.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
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 account representative. 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 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.
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.
CPT codes are provided by the performing laboratory.
81449
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| 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 |