Test Id : NONCM

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.

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 20% tumor nuclei.

-Preferred amount of tumor area with sufficient percent tumor nuclei: tissue 288 mm(2)

-Minimum amount of tumor area: tissue 36 mm(2)

-If ordered in conjunction with CMAPT / Chromosomal Microarray, Tumor, Formalin-Fixed Paraffin-Embedded, the preferred amount of tissue is 430 mm(2), the minimum amount is 180 mm(2).

-These amounts are cumulative over up to 15 unstained slides and must have adequate percent tumor nuclei.

-Tissue fixation: 10% neutral buffered formalin, not decalcified

- For this test, at least 6 mm x 6 mm areas on 8 unstained slides is preferred: this is approximately equivalent to 288 mm(2). The minimum acceptable area is 6 mm x 6 mm on 1 unstained slides: approximately equivalent to 36 mm(2). For specimen preparation guidance, see Tissue Requirement for Solid Tumor Next-Generation Sequencing.

Preferred:

Specimen Type: Tissue block

Collection Instructions: Submit a formalin-fixed, paraffin-embedded tissue block with acceptable amount of tumor tissue.

Acceptable:

Specimen Type: Tissue slide

Slides: 1 Hematoxylin and eosin-stained and 15 unstained

Collection Instructions:

Submit the following slides:

1 Slide stained with hematoxylin and eosin

AND

15 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 15 slides from the same block.

Additional information: Unused unstained slides will not be returned.

• Targeted DNA Gene Regions Interrogated by Neuro-Oncology Panel
• Tissue Requirements for Solid Tumor Next-Generation Sequencing

See Specimen Required

Identifying mutations that may support a diagnosis or help determine prognosis for patients with central nervous system tumors

Identifying specific mutations within genes known to be associated with response or resistance to specific cancer therapies

This test is not intended for use for hematological malignancies.

This test uses next-generation sequencing to evaluate for microsatellite instability (MSI) status and somatic mutations involving 89 genes associated with tumors of the central nervous system. See Targeted DNA Gene Regions Interrogated by Neuro-Oncology Panel for details regarding the targeted gene regions identified by this test.

Of note, this test is performed to evaluate for somatic (ie, tumor-specific) mutations within the genes listed. Although germline (ie, inherited) alterations may be detected, this test cannot distinguish between germline and somatic alterations with absolute certainty. Follow-up germline testing using non-neoplastic (normal) tissue can be performed for confirmation of suspected clinically relevant germline alterations. Germline testing should be performed along with genetic counseling.

This test only evaluates MSI status and somatic mutations; this test does not evaluate for rearrangements (fusions and abnormal transcript variants).

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

Molecular biomarkers, including clinically relevant gene mutations (ie, sequence variants), have been incorporated in the World Health Organization classification of central nervous system (CNS) tumors. Additionally, there are clinically available targeted therapies for patients with certain CNS tumor types harboring specific mutations. This test evaluates targeted regions across 89 genes associated with a variety of adult and pediatric-type CNS tumors for the presence of somatic mutations including, but not limited to, mutations in IDH1/2, TERT promoter, ATRX, TP53, H3-3A (previously H3F3A), H3C2/H3C3 (previously HIST1H3B/C), BRAF, FGFR1, NF1 and SMARCB1.

See Targeted DNA Gene Regions Interrogated by Neuro-Oncology Panel for details regarding the targeted gene regions identified by this test.

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 does not include evaluation of rearrangements (fusions and abnormal transcript variants).

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.

Variants of uncertain significance may be identified.

A negative result does not rule out the presence of a variant that may be present below the limits of detection of this assay. The analytical sensitivity of this assay for sequence reportable alterations is 5% mutant allele frequency with a minimum coverage of 500X in a sample with 20% or more tumor content.

Point mutations and small insertion/deletion mutations will be detected in 89 genes. This test may detect single exon deletions but does not detect multi-exon deletions, duplications, or genomic copy number variants in any of the genes tested

The presence or absence of a variant may not be predictive of response to therapy in all patients.

Rare alterations (ie, polymorphisms) may be present that could lead to false-negative or false-positive results.

Test results should be interpreted in the context of clinical, tumor sampling, histopathological, and other laboratory data. If results obtained do not match other clinical or laboratory findings, contact the laboratory for discussion. 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 formalin-fixed, paraffin-embedded tissues; other fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause polymerase chain reaction failure.

Genes may be added or removed based on updated clinical relevance. Refer to the Targeted DNA Gene Regions Interrogated by Neuro-Oncology Panel for the most up to date list of genes included in this test.

Performance Characteristics

The limit of detection for calling a somatic variant (single nucleotide variants [SNV] and deletions-insertions [delins]) is 5% variant allele frequency (VAF) and having at least 500x deduplicated coverage.

Verification studies demonstrated concordance between this test and the reference method for detection of SNV and delins is 99.7% (699/701) and 96.6% (226/234) of variants, respectively. Concordance for the detection of delins was 98.9% (186/188) in variants 1 to 10 base pairs (bp) in size, 95.8% (23/24) in variants 11 to 50 bp in size, and 88.9% (8/9) in variants 51 to 200 bp in size.

Microsatellite instability (MSI) evaluation is accurate at a tumor purity of at least 10% for colorectal tumors and 20% for other tumor types. During verification studies, 98% (200/204) concordance for MSI status was observed between this test and the reference method.

To ensure accuracy, this test will be performed on cases estimated by a pathologist to have at least 20% tumor cells.

1. Schwartzentruber J, Korshunov A, Liu XY, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012;482(7384):226-231

2. Zhang J, Wu G, Miller CP, et al. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat Genet. 2013;45(6):602-612

3. Jones DT, Hutter B, Jager N, et al. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat Genet. 2013;45(8):927-932

4. Brennan CW, Verhaak RG, McKenna A, et al. The somatic genomic landscape of glioblastoma. Cell. 2013;155(2):462-477

5. Brastianos PK, Horowitz PM, Santagata S, et al. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet. 2013;45(3):285-289

6. Clark VE, Erson-Omay EZ, Serin A, et al. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science. 2013;339(6123):1077-1080

7. Wu G, Diaz AK, Paugh BS, et al. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet. 2014;46(5):444-450

8. Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, et al. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med. 2015;372(26):2481-2498

9. Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015 25;372(26):2499-2508

10. Ceccarelli M, Barthel FP, Malta TM, et al. Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell. 2016;164(3):550-563

11. Pajtler KW, Mack SC, Ramaswamy V, et al. The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants. Acta Neuropathol. 2017;133(1):5-12

12. Northcott PA, Buchhalter I, Morrissy AS, et al. The whole-genome landscape of medulloblastoma subtypes. Nature. 2017;547(7663):311-317

13. WHO Classification of Tumours Editorial Board: Central Nervous System Tumours. 5th ed. World Health Organization; 2021. WHO Classification of Tumours. Vol 6.

14. Nabors LB, Portnow J, Ammirati M, et al. Central nervous system cancers version 1.2015. J Natl Compr Canc Netw. 2015;13(10);1191-1202

Hybridization and capture-based next-generation sequencing (NGS) are performed to determine microsatellite instability (MSI) status and evaluate the presence of a mutation in targeted regions of 89 genes.

See Targeted DNA Gene Regions Interrogated by Neuro-Oncology Panel for details regarding the targeted gene regions identified by this test.(Unpublished Mayo method)

A pathology review and macro dissection to enrich for tumor cells is 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.

81455