Test Id : MCRSP

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

Multiple oncology (cancer) gene panels are available. For more information see Hematology, Oncology, and Hereditary Test Selection Guide.

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

5. Diagnosis, potential diagnosis, or differential diagnoses

This assay requires at least 10% tumor nuclei.

-Preferred amount of tumor area with sufficient percent tumor nuclei: tissue 144 mm(2)

-Minimum amount of tumor area: tissue 36 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

-For specimen preparation guidance, see Tissue Requirements for Solid Tumor Next-Generation Sequencing. In this document, the sizes are given as 4 mm x 4 mm x 10 slides as preferred: approximate/equivalent to 144 mm(2) and the minimum as 3 mm x 1 mm x 10 slides: approximate/equivalent to 36 mm(2).

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 slides

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 slides (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.

• Tissue Requirements for Solid Tumor Next-Generation Sequencing
• Targeted Fusion Genes for MayoComplete Targeted RNAseq Panel

See Specimen Required

Primarily for identifying gene fusions that help in the diagnosis of solid tumors

Secondarily, for identifying gene fusions that have therapeutic or prognostic significance

This test uses next-generation sequencing to evaluate 1445 genes for the presence of somatic gene fusions, known abnormal transcript variants in the MET and EGFR genes, and BCOR exon 15 internal tandem duplications. See Targeted Fusion Genes for MayoComplete Targeted RNAseq Panel for details regarding the targeted gene regions evaluated by this test.

This test is performed to evaluate for somatic gene fusions within solid tumor samples. It does not assess for germline alterations.

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

Molecular analysis of biomarkers is increasingly being utilized in oncology practices to support and guide diagnosis, prognosis, and therapeutic management of patients.

This next-generation sequencing assay interrogates 1445 genes for the presence of gene fusions that can result from chromosomal translocations, interstitial deletions, and inversions, that have clinical implications for diagnosis, prognosis and therapy in solid tumors.

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 assay is not validated for the detection of single nucleotide variations, deletions-insertions, copy number alterations, or gene expression.

Fusions of uncertain significance may be identified.

The sensitivity of this assay for gene fusions depends on several variables including decreased sensitivity with decreased tumor percentage, and decreased sensitivity with decreased level of expression of a variant.  A negative result does not rule out the presence of a gene fusion, splice variant, or BCOR exon 15 internal tandem duplication that may be present but below the limits of detection of this assay. The analytical sensitivity of this assay is a minimum coverage of 5 unique variant molecules in a sample with at least 10% tumor content.

This assay can detect in-frame and out-of-frame fusions involving 1445 genes. Sensitivity for detecting out-of-frame fusions, such as exon-intron, intron-intron or big insertions, may be lower due to bioinformatics detection limitations. This assay will only detect fusions involving at least 1 gene in the defined gene fusion target list of interest. This assay may not detect fusions involving deep intron or intergenic regions and will not detect chromosomal rearrangements that do not create a fusion transcript (ie, enhancer repositioning). Variants not expressed, or expressed at very low level, are not detected by this assay.

Rare variants, or alterations derived from the production of a gene fusion, may be present that could lead to false-negative or false-positive results.

The presence or absence of a fusion 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 an 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.

RNA is particularly labile and degrades quickly. Rapid preservation of the tumor sample after collection reduces the likelihood of degradation. Still, there can be biological factors, such as tumor necrosis, which interfere with obtaining a high-quality RNA specimen despite rapid preservation.

Performance Characteristics:

Validation studies demonstrated that concordance between this test, and the reference method, for detection of gene fusions, BCOR in-tandem duplications, and splice variants within MET and EGFR is 96.6% (256/265). No gene fusions were detected in 14 normal tissues, and no gene fusions were detected in the negative control sample (100% specificity).

To ensure that this assay detects fusions based on the established sensitivity, this test will be performed on cases that are estimated by a pathologist to have at least 10% tumor cells.

1. Jennings LJ, Arcila ME, Corless C, et al. Guidelines for validation of next-generation sequencing-based oncology panels: a joint consensus recommendation of the Association for Molecular Pathology and College of American Pathologists. J Mol Diagn. 2017;19(3);341-365

2. US Food and Drug Administration (FDA): Table of Pharmacogenomic Biomarkers in Drug Labeling. FDA; Updated February 10, 2023, Accessed August 1, 2023. Available at www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling

3. Sbaraglia M, Bellan E, Dei Tos AP. The 2020 WHO Classification of Soft Tissue Tumours: news and perspectives. Pathologica. 2021;113(2):70-84. doi:10.32074/1591-951X-213

4. RNA-seq with exome fusion detection technical note.Doc ID: RUO22-0858_001.Integrated DNA Technologies; 05/22

5. Michuda J. et al., Use of clinical RNA-sequencing in the detection of actionable fusions compared to DNA-sequencing alone. J Clin Oncol. 2022;40(Suppl 16):3077-3077. doi:10.1200/JCO.2022.40.16_suppl.3077.

6. Li W, Guo L, Liu Y, et al. Potential Unreliability of Uncommon ALK, ROS1, and RET Genomic Breakpoints in Predicting the Efficacy of Targeted Therapy in NSCLC. J Thorac Oncol. 2021;16(3):404-418

7. Gao Q, Liang WW, Foltz SM, et al. Driver Fusions and Their Implications in the Development and Treatment of Human Cancers. Cell Rep. 2018;23(1):227-238e3. doi:10.1016/j.celrep.2018.03.050

8. Roy A, Kumar V, Zorman B, et al. Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. Nat Commun. 2015;6:8891. doi:10.1038/ncomms9891

9. Marino-Enriquez A, Lauria A, Przybyl J, et al. BCOR internal tandem duplication in high-grade uterine sarcomas. Am J Surg Pathol. 2018;42(3):335-341. doi:10.1097/PAS.0000000000000993

10. Parimi V, Tolba K, Danziger N, et al. Genomic landscape of 891 RET fusions detected across diverse solid tumor types. NPJ Precis Oncol. 2023;7(1);10

11. Marcus L, Donoghue M, Aungst S, et al. FDA Approval Summary: Entrectinib for the Treatment of NTRK gene Fusion Solid Tumors. Clin Cancer Res. 2021;27(4):928-932

12. Mehra R, Tomlins SA, Yu J, et al. Characterization of TMPRSS2-ETS gene aberrations in androgen-independent metastatic prostate cancer. Cancer Res. 2008;68(10):3584-3590

13. Hu H, Mu Q, Bao Z, et al. Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor. Cell. 2018;175(6):1665-1678 e18

14. Lei JT, Gou X, Seker S, Ellis MJ. ESR1 alterations and metastasis in estrogen receptor positive breast cancer. J Cancer Metastasis Treat, 2019;5:38

15. Liu SV, Nagasaka M, Atz J, Solca F, Mullauer L. Oncogenic gene fusions in cancer: from biology to therapy. Signal Transduct Target Ther. 2025;10(1):111 doi:10.1038/s41392-025-02161-7

RNA-based next-generation sequencing is performed to test for the presence of rearrangements involving 1445 genes, selected splice variants in MET and EGFR genes, and internal tandem duplications within exon 15 of the BCOR gene. See Targeted Fusion Genes for MayoComplete Targeted RNAseq Panel for details regarding the targeted gene regions evaluated by this test genes.(Unpublished Mayo method)

A pathology review and macro dissection to enrich for tumor cells are performed prior to slide scraping.

Monday through Friday

• 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.

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.

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