Identifying mutations and rearrangements that may support a diagnosis for patients with tumors of the central nervous system (CNS)
Identifying mutations and rearrangements that may help determine prognosis for patients with tumors of the CNS
Identifying specific mutations and rearrangements within genes known to be associated with response or resistance to specific cancer therapies
This test uses targeted next-generation sequencing to evaluate for somatic mutations and rearrangements (fusions and abnormal transcript variants) involving 187 genes associated with tumors of the central nervous system. This panel includes a DNA subpanel for the detection of sequence alterations in 118 genes and an RNA subpanel for the detection of rearrangements in 81 genes, including 104 known gene fusions and 29 known abnormal transcript variants. See Targeted DNA Gene Regions Interrogated by Neuro-Oncology Panel and RNA Targeted Gene Fusions and Abnormal Transcript Variants in Special Instructions 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 counselling.
This next-generation sequencing tumor profiling assay interrogates targeted gene regions and rearrangements across 187 genes associated with central nervous system tumors to assess for the presence of somatic mutations and rearrangements, including mutations in IDH1/2, TERT, ATRX, TP53, H3F3A, HIST1H3B/C, BRAF, SMARCB1, and SMARCA4, and rearrangements involving RELA, BRAF, and EGFR (eg, EGFR vIII).
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
SLIRV | Slide Review in MG | No, (Bill Only) | Yes |
When this test is ordered, slide review will always be performed at an additional charge.
Polymerase Chain Reaction (PCR)-Based Next-Generation Sequencing (NGS)
ATRX
BRAF
Brain tumor
Central nervous system (CNS) cancers
EGFR
H3F3A
HIST1H3B
HIST1H3C
IDH1
IDH2
Next Gen Sequencing Test
NGS
Oncology panel
RELA
SMARCA4
SMARB1
TERT
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 Oncology Somatic NGS Testing Guide.
Pathology report (final or preliminary) at minimum containing the following information must accompany specimen in order 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 30% tumor nuclei.
-Preferred amount of tumor area with sufficient percent tumor nuclei: tissue 360 mm(2)
-Minimum amount of tumor area: tissue 144 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 10 unstained slides and must have adequate percent tumor nuclei.
-Tissue fixation: 10% neutral buffered formalin, not decalcified
-For specimen preparation guidance, see Tissue Requirement for Solid Tumor Next-Generation Sequencing in Special Instructions. For this test, 6mm x 6mm x 10 slides is preferred: approximate/equivalent to 360 mm(2) with the minimum acceptable of 4mm x 4mm x 10 slides: approximate/equivalent to 144mm(2).
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 stained and 15 unstained
Collection Instructions: Submit 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: If the amount of tissue available is close to the minimum required, the ordering provider may be asked to prioritize between the DNA and RNA components of the assay.
If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.
See Specimen Required
Specimens that have been decalcified (all methods) Specimens that have not been formalin-fixed, paraffin-embedded | Reject |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Ambient (preferred) | ||
Frozen | |||
Refrigerated |
Identifying mutations and rearrangements that may support a diagnosis for patients with tumors of the central nervous system (CNS)
Identifying mutations and rearrangements that may help determine prognosis for patients with tumors of the CNS
Identifying specific mutations and rearrangements within genes known to be associated with response or resistance to specific cancer therapies
This test uses targeted next-generation sequencing to evaluate for somatic mutations and rearrangements (fusions and abnormal transcript variants) involving 187 genes associated with tumors of the central nervous system. This panel includes a DNA subpanel for the detection of sequence alterations in 118 genes and an RNA subpanel for the detection of rearrangements in 81 genes, including 104 known gene fusions and 29 known abnormal transcript variants. See Targeted DNA Gene Regions Interrogated by Neuro-Oncology Panel and RNA Targeted Gene Fusions and Abnormal Transcript Variants in Special Instructions 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 counselling.
When this test is ordered, slide review will always be performed at an additional charge.
Molecular analysis of biomarkers is increasingly being used in oncology practice to support and guide diagnosis, prognosis, and therapeutic management. Molecular profiling has been incorporated in the World Health Organization classification of central nervous system (CNS) tumors and allows for robust delineation of diagnostic groups characterized by distinct molecular profiles with superior prognostic significance than histopathological classification alone. This test interrogates targeted regions across 187 genes associated with a variety of adult and pediatric CNS tumors to assess for the presence of somatic mutations and rearrangements, including mutations in IDH1/2, TERT, ATRX, TP53, H3F3A, HIST1H3B/C, BRAF, SMARCB1, and SMARCA4, and rearrangements involving RELA, BRAF, and EGFR (eg, EGFR vIII).
See Targeted Gene Regions Interrogated by Neuro-Oncology Panel in Special Instructions for details regarding the targeted gene regions identified by this test.
An interpretive report will be provided.
An interpretive report will be provided.
This test is not designed to differentiate between somatic and germline alterations. Additional testing may be necessary to clarify the significance of results if there is a potential hereditary risk.
DNA variants of uncertain significance may be identified.
A negative (wild-type) result does not rule out the presence of a mutation or rearrangement that may be present but below the limits of detection of this assay. The analytical sensitivity of this assay for sequence reportable alterations is 15% mutant allele frequency with a minimum coverage of 100 times in a sample with 30% or greater tumor content, and for rearrangements is a minimum coverage of 10 targeted fusion reads with 5 unique fusion molecules in a sample with 10% or greater tumor content.
This test does not detect large single or multiexon deletions or duplications or genomic copy number alterations
Rare polymorphisms may be present that could lead to false-negative or false-positive results. 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 discussion of the findings. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.
Genes may be added or removed based on updated clinical relevance. Please refer to the Targeted DNA Gene Regions Interrogated by Neuro-Oncology Panel in Special Instructions for the most up to date list of genes included in this test.
Detection of somatic mutations (DNA):
Detection of fusion transcripts (RNA): The RNA fusion portion of the test exhibited 94.2% sensitivity (49/52) in detecting fusion transcripts (confirmed detection by reverse transcriptase polymerase chain reaction or chromosomal microarray). No fusion transcripts were detected in 25 unique samples (100% specificity compared to chromosomal microarray) resulting in an overall concordance of 96.1%.
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 N, 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;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. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, eds: WHO Classification of Tumours of the Central Nervous System. Revised 4th ed. IARC; 2016
14. Nabors LB, Portnow J, Ammirati M, et al: Central nervous system cancers version 1.2015. J Natl Compr Canc Netw. 2015 Oct;13(10);1191-1202
Next-generation sequencing (NGS) is performed to test for the presence of a mutation in approximately 95% of exonic regions and exon/intron boundaries of 118 targeted genes. NGS is performed to test for the presence of rearrangements in 81 genes, including 104 known gene fusions and 29 known abnormal gene transcript variants. See Targeted DNA Gene Regions Interrogated by Neuro-Oncology Panel and RNA Targeted Gene Fusions and Abnormal Transcript Variants in Special Instructions for details regarding the targeted gene regions identified by this test.(Unpublished Mayo method)
Monday through Friday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
81455
88381
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
NONCP | Neuro-Onc Expanded Panel | 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.
|
---|---|---|
603048 | Result Summary | 50397-9 |
603049 | Result | 82939-0 |
603050 | Interpretation | 69047-9 |
603051 | Additional Information | 48767-8 |
603052 | Specimen | 31208-2 |
603053 | Source | 31208-2 |
603054 | Tissue ID | 80398-1 |
603055 | Released By | 18771-6 |
Change Type | Effective Date |
---|---|
Test Status - Test Delay | 2023-01-23 |
Test Status - Test Resumed | 2021-07-12 |
Test Status - Test Delay | 2021-05-21 |
Test Status - Test Resumed | 2021-05-06 |