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Test Code IDHT IDH1 and IDH2 Mutation Analyses, Next-Generation Sequencing, Tumor


Ordering Guidance


If this test is ordered with TERTD / TERT Promoter Mutation Analysis, Droplet Digital PCR, Tumor, this test will be canceled and IDTRT / IDH1, IDH2, and TERT Mutation Analysis, Next-Generation Sequencing, Tumor will be ordered.

 

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


This assay requires at least 20% tumor nuclei.

-Preferred amount of tumor area with sufficient percent tumor nuclei: tissue 216 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:

Specimen Type: Tissue block

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

 

Acceptable:

Specimen Type: Tissue slides

Slides: 1 Stained and 10 unstained

Collection Instructions: Submit 1 slide stained with hematoxylin and eosin and 10 unstained, nonbaked slides wit 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 preferred total of 5000 nucleated cells, or a minimum of at least 3000 nucleated cells.

Note: Glass coverslips are preferred; plastic coverslips are acceptable but will result in longer turnaround times.

Additional Information: Cytology slides will not be returned.


Secondary ID

616498

Useful For

Identifying specific mutations within the IDH1 and IDH2 genes that assist in tumor diagnosis/classification and predict response to targeted therapy

Additional Tests

Test ID Reporting Name Available Separately Always Performed
SLIRV Slide Review in MG No, (Bill Only) Yes

Testing Algorithm

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

Method Name

Sequence Capture and Targeted Next-Generation Sequencing (NGS)

Reporting Name

IDH1/IDH2 Mutations Analysis, Tumor

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
  Refrigerated 

Reject Due To

Specimens that have been decalcified (all methods)
Specimens that have not been formalin-fixed, paraffin-embedded, except for cytology slides
Extracted nucleic acid (DNA/RNA)		 Reject

Clinical Information

IDH1 and IDH2 (isocitrate dehydrogenase: IDH) genes encode enzymes involved in cellular glucose metabolism. Mutations in the IDH genes primarily involve codons R132 in IDH1 and R140 and R172 in IDH2 and lead to the neomorphic ability to generate oncometabolite R(-)-2-hydroxyglutarate, which contributes to tumorigenesis. In central nervous system (CNS) tumors, IDH mutations are a diagnostic molecular biomarker for diffuse gliomas and define two biologically distinct groups: IDH-mutant and IDH-wildtype tumors. IDH mutations are rarely observed in other CNS tumor types and are not seen in CNS reactive non-neoplastic processes. IDH mutations are also a molecular biomarker in non-CNS tumors, including acute myeloid leukemia, cholangiocarcinoma, and cartilaginous tumors. Clinically approved targeted therapies are available for a subset of patients with IDH-mutant acute myeloid leukemia and IDH-mutant cholangiocarcinoma.

Reference Values

An interpretive report will be provided.

Interpretation

The interpretation of molecular biomarker analysis includes an overview of the results and the associated diagnostic, prognostic, and therapeutic implications.

Cautions

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.

 

DNA variants of uncertain significance may be identified.

 

A negative result does not rule out the presence of a variant that may be present but 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 the IDH1 and IDH2 genes only. This test may detect single exon deletions but does not detect multi-exon deletions, duplications or genomic copy number variants.

 

Variant allele frequency (VAF) is the percentage of sequencing reads supporting a specific variant divided by the total sequencing reads at that position. In somatic testing, VAF should be interpreted in the context of several factors including, but not limited to: tumor purity/heterogeneity/copy number status (ploidy, gains/losses, loss of heterozygosity) and sequencing artifact/misalignment.(1,2)

 

Rare 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, 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 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.

Supportive Data

Performance Characteristics:

The limit of detection for calling a somatic variant (single nucleotide variants [SNV] and deletions/insertions [delins, formerly indels]) is 5% variant allele frequency 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.

Clinical Reference

1. Strom SP. Current practices and guidelines for clinical next-generation sequencing oncology testing. Cancer Biol Med. 2016;13(1):3-11. doi:10.28092/j.issn.2095-3941.2016.0004

2. Spurr L, Li M, Alomran N, et al. Systematic pan-cancer analysis of somatic allele frequency. Sci Rep. 2018;8(1):7735. Published 2018 May 16. doi:10.1038/s41598-018-25462-0

3. US Food and Drug Administration (FDA): Table of Pharmacogenomic Biomarkers in Drug Labeling. FDA; Updated February, 10, 2023, Accessed July 31, 2023. Available at www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling

4. WHO Classification of Tumours Editorial Board: Central nervous system tumours. 5th ed. World Health Organization; 2021. WHO Classification of Tumours. Vol 6.

5. Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360(8):765-773

6. 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

7. 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

8. Mardis ER, Ding L, Dooling DJ, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med. 2009;361(11):1058-1066

9. Jusakul A, Cutcutache I, Yong CH, et al. Whole-genome and epigenomic landscapes of etiologically distinct subtypes of cholangiocarcinoma. Cancer Discov. 20177(10):1116-1135

10. Amary MF, Bacsi K, Maggiani F, et al. IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J Pathol. 2011;224(3):334-343

Method Description

Next-generation sequencing is performed to evaluate the presence of a mutation in all coding regions of the IDH1 and IDH2 genes. See Targeted Genes and Methodology Details for IDH1/IDH2 Mutation Analysis 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 is performed prior to slide scraping.

Day(s) Performed

Monday through Friday

Report Available

12 to 20 days

Specimen Retention Time

FFPE tissue block: Unused portions of blocks will be returned within 10-14 days after testing is complete; FFPE tissue/cytology slides: Unused tissue slides are stored indefinitely; Digital images are obtained and stored for all slides used in testing

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

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

88381-Microdissection, manual

81479

LOINC Code Information

Test ID Test Order Name Order LOINC Value
IDHT IDH1/IDH2 Mutations Analysis, Tumor 104323-1

 

Result ID Test Result Name Result LOINC Value
617913 Result 82939-0
617914 Interpretation 69047-9
617915 Additional Information 48767-8
617916 Specimen 31208-2
617917 Tissue ID 80398-1
617918 Method 85069-3
617919 Disclaimer 62364-5
617920 Released By 18771-6

Forms

If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.