Test Catalog

Test ID: NONCP    
Neuro-Oncology Expanded Panel with Rearrangement, Tumor

Useful For Suggests clinical disorders or settings where the test may be helpful

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

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test uses targeted next-generation sequencing to evaluate for somatic mutations and rearrangements (fusions and abnormal transcript variants) involving 219 genes associated with tumors of the central nervous system. This panel includes a DNA subpanel for the detection of sequence alterations in 150 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.

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

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 WHO 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 219 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.

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

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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.

Supportive Data

Detection of somatic mutations (DNA): The DNA mutation portion of the assay has been shown to detect more than 97% of single base substitutions, insertions, and deletions within the reportable range of this assay.

 

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 PCR 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%.

Clinical Reference Recommendations for in-depth reading of a clinical nature

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. WHO Classification of Tumours of the Central Nervous System. Revised fourth edition. Edited by DN Louis, H Ohgaki. OD Wiestler, WK Cavenee. IARC: Lyon 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

Special Instructions Library of PDFs including pertinent information and forms related to the test