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HelpTest Code XL2T FOXL2 Mutation Analysis, Next-Generation Sequencing, Tumor
Ordering Guidance
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 Requirement 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 slide
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 slide (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.
Useful For
Assisting in the clinical diagnosis of adult granulosa cell tumor by assessing gene targets within the FOXL2 gene
Genetics Test Information
This test uses targeted next-generation sequencing to evaluate for somatic mutations within the FOXL2 gene.
This test is performed to evaluate for somatic mutations within solid tumor samples. It does not assess germline alterations within the region tested.
Highlights
This test evaluates formalin-fixed, paraffin-embedded tumor or cytology slides to assist in the clinical diagnosis of adult granulosa cell tumor.
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
FOXL2 Mutations Analysis, TumorSpecimen Type
VariesSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Ambient (preferred) | |
| Refrigerated | ||
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
Granulosa cell tumors (GCT) represent approximately 5% to 10% of all ovarian malignancies and are the most common type of malignant ovarian sex-cord stromal tumors. The majority of GCT (95%) are adult type and 5% are juvenile type. Adult GCT can occur at any age but most commonly occur in perimenopausal women, whereas juvenile GCT arise in the first 3 decades of life. FOXL2 (forkhead box L2) gene is involved in ovarian development and function. The FOXL2 gene point mutation c.402C>G in exon 1 (p.C134W) has been reported in the majority of adult GCT (>90%), one molecular subtype of Sertoli-Leydig cell tumor, and rarely also in thecomas. In cases with challenging histopathology, detection of a FOXL2 mutation can aid in the clinical diagnosis of adult GCT.
This test uses formalin-fixed paraffin-embedded tissue or cytology slides to assess for the common somatic hotspot mutations in the FOXL2 gene. The results of this test can be useful for supporting a diagnosis of adult GCT.
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 mutations 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 deletion-insertion (delins) mutations will be detected in the FOXL2 gene only. This test may detect single exon deletions but does not detect multi-exon deletions, duplications, larger-scale genomic copy number variants, copy neutral loss of heterozygosity, or epigenetic modifications such as promoter methylation. Delins of 1000 base pairs or less are detectable with at least 50 or more supporting reads.
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 genetic alterations (ie, 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.
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. Shah SP, Kobel M, Senz J, et al. Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med. 2009;360(26):2719-2729
4. Kim MS, Hur SY, Yoo NJ, Lee SH. Mutational analysis of FOXL2 codon 134 in granulosa cell tumour of ovary and other human cancers. J Pathol. 2010;221(2):147-152
5. Schrader KA, Gorbatcheva B, Senz J, et al. The specificity of the FOXL2 c.402C>G somatic mutation: a survey of solid tumors. PLoS One. 2009;4(11):e7988
6. Benayoun BA, Kalfa N, Sultan C, Veitia RA. The forkhead factor FOXL2: a novel tumor suppressor? Biochim Biophys Acta. 2010;1805(1):1-5
7. WHO Classification of Tumours Editorial Board: Female genital tumours. 5th ed. World Health Organization; 2021. WHO Classification of Tumours. Vol 4.
Day(s) Performed
Monday through Friday
Report Available
12 to 20 daysSpecimen Retention Time
Tissue blocks: Unused portions of blocks will be returned; Tissue slides: Unused slides are stored for at least 5 years; Extracted DNA: 3 monthsPerforming 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 |
|---|---|---|
| XL2T | FOXL2 Mutations Analysis, Tumor | 95785-2 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 617937 | Result | 82939-0 |
| 617938 | Interpretation | 69047-9 |
| 617939 | Additional Information | 48767-8 |
| 617940 | Specimen | 31208-2 |
| 617941 | Tissue ID | 80398-1 |
| 617942 | Method | 85069-3 |
| 617943 | Disclaimer | 62364-5 |
| 617944 | Released By | 18771-6 |
Forms
If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.