Test Catalog

Test ID: XL2    
FOXL2 Mutation Analysis, Tumor

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

Assisting in the clinical diagnosis of adult granulosa cell tumor (GCT) by assessing gene targets with in the FOXL2 gene


This test is not useful for hematological malignancies.

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

Granulosa cell tumor (GCT) represents approximately 5% to 10% of all ovarian malignancies and is the most common type of malignant ovarian sex-cord stromal tumor. The majority of patients with GCT (95%) are adults and 5% are juveniles. The histopathological diagnosis of GCT is challenging. Forkhead box L2 (FOXL2) gene is involved in ovarian development and function. The FOXL2 gene point mutation 402C->G in exon 1 (C134W) was reported in the majority of adult GCT (>90%), 5% to 10% of thecomas (tumors closely related to GCT) and less than 10% of juvenile GCT cases, but not in other ovarian tumors. Detection of FOXL2 mutation aids in the clinical diagnosis of adult GCT.


Next-generation sequencing has recently emerged as an accurate, cost-effective method to identify alterations across numerous genes. This test uses formalin-fixed paraffin-embedded tissue or cytology slides to assess for common somatic mutations in the FOXL2 gene known to be associated with adult GCT. The results of this test can be useful for supporting a diagnosis of adult GCT.

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 interpretative 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 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 (wild-type) result does not rule out the presence of a mutation that may be present but below the limits of detection of this assay.


Point mutations and small insertion and deletion mutations will be detected with in the FOXL2 gene only. This test does not detect large single or multiexon deletions, or duplications or genomic copy number variants.


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, please contact the laboratory for updated interpretation. 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 PCR failure.

Supportive Data

This next-generation sequencing assay detects somatic mutations that can be used to assist in the diagnosis of granulosa cell tumor (GCT).


This assay has been shown to be very reproducible, having a 100% concordance for intra- and interassay reproducibility experiments. All somatic mutations that had been previously identified by various other molecular methods were detected by this assay during accuracy studies. No pathogenic variants were detected in known mutation-negative samples.

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

1. Shah SP, Kobel M, Senz J, et al: Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med 2009;360:2719-2729

2. Kim MS, Hur SY, Yoo NJ, et al: Mutational analysis of FOXL2 codon 134 in granulosa cell tumour of ovary and other human cancers. J Pathol 2010;221:147-152

3. 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 Nov 24;4(11):e7988

4. Benayoun BA, Kalfa N, Sultan C, et al: The forkhead factor FOXL2: a novel tumor suppressor? Biochim Biophys Acta 2010;1805:1-5

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