TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: SARCP    
Sarcoma Targeted Gene Fusion/Rearrangement Panel, Next-Generation Sequencing, Tumor

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

Diagnosing specific soft tissue and bone tumors (sarcoma) based on the observed gene fusions (eg, PAX3/FOXO1 gene fusion observed in alveolar rhabdomyosarcoma, EWSR1-FLI1 gene fusion for Ewing’s sarcoma, SS18-SSX1/2 gene fusion for synovial sarcoma)

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

This test evaluates 138 gene targets for the presence of somatic gene fusions and also assesses for common BCOR internal tandem duplications. See Sarcoma Targeted Gene Fusion Panel and Common BCOR Tandem Duplications in Special Instructions for details regarding the targeted gene regions identified by this test.

 

Targeted genes: ACTB, AHRR, ALK, ASPSCR1, ATF1, ATIC, BCOR, BRD3, BRD4, CAMTA1, CARS, CCNB3, CDH11, CDX1, CD63, CEP128, CIC, CITED2, CLTC, CNBP, COL1A1, COL1A2, COL3A1, COL6A3, CREB1, CREB3L1, CREB3L2, CSF1, CXorf67, C11orf95, DDIT3, DUX4, DVL2, EML4, EPC1, EP400, ERG, ETV1, ETV4, ETV6, EWSR1, FEV, FGFR1, FLI1, FN1, FOSB, FOXO1, FOXO4, FUS, GLI1, HAS2, HEY1, HMGA2, IRF2BP2, JAZF1, KIRREL, KLF17, LAMTOR1, LPP, MAML3, MBTD, MEAF6, MED12, MIR143HG, MKL2, MYH9, NAB2, NCOA1, NCOA2, NFATC2, NFIB, NOTCH1, NOTCH2, NR4A3, NTRK1, NTRK3, NUMA1, NUTM1, NUTM2B, OMD, OPHN1, PATZ1, PAX3, PAX7, PBX1, PBX3, PDGFB, PDPN, PHF1, PLAG1, PLPP3, POU5F1, PPFIBP1, PRDM10, PRKCA, PRKCB, PRKCD, RAB2A,RAD51B, RANBP2, RNF213, RRAGB, SEC31A, SERPINE1, SETBP1, SFMBT1, SMARCA5, SP3, SQSTM1, SRF, SRSF3, SSX1, SSX2, SSX4, SS18, SS18L1, STAT6, SUZ12, S100A10, TAF15, TCF12, TEAD1, TFE3, TFG, THRAP3, TPM3, TPM4, TPR, USP6, VCL, VGLL2, WT1, WWTR1, YAP1, YWHAE, ZC3H7B, ZFP36, and ZNF444.

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 utilized in oncology practices to support and guide diagnosis, prognosis, and therapeutic management of patients. Chromosomal translocations, interstitial deletions, and inversions that lead to gene fusions are common in various sarcomas such as Ewing sarcoma and rhabdomyosarcoma. This next-generation sequencing assay is used to detect specific gene fusions to assist in the diagnosis of sarcomas. See Sarcoma Targeted Gene Fusion 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 assay is not validated for the detection of point variations, indels, copy number alterations, or gene expression.

 

This assay may detect gene fusions that are present at the RNA level, but not the DNA level, that result from cis-splicing of adjacent genes or trans-splicing.(1)

 

This panel can detect in-frame and out-of-frame fusions. There may be lower sensitivity in detecting out-of-frame fusions such as exon-intron, intron-intron or big insertions. This assay will only detect fusions involving at least 1 gene in the defined genes of interest list.

 

This assay will only detect fusions involving gene transcripts that have been defined in UCSC Genome Browser (March 2012 version) available from Illumina's iGenomes Project.(2)

 

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.

 

A negative result does not rule out the presence of a gene fusion that may be present but below the limits of detection of this assay (tumor cells comprise <10% of the cell population; targeted fusion read coverage with <10 unique fusion molecules in a sample).

 

The limit of detection of this assay for specific gene fusions is dependent on a number of variables including decreased sensitivity with decreased tumor percentage and decreased sensitivity with decreased level of expression of the gene fusion.

 

RNA is particularly labile and degrades quickly. Rapid preservation of the tumor sample after collection reduces the likelihood of degradation but there are sometimes biological factors such as tumor necrosis which interfere with obtaining a high quality RNA specimen despite rapid preservation.

 

The presence or absence of a fusion may not be predictive of response to therapy or prognosis in all patients.

 

Fusions of uncertain significance may be identified.

Supportive Data

In a verification study, this next-generation sequencing (NGS) assay was performed in 111 sarcoma formalin-fixed, paraffin-embedded (FFPE) and cytology samples (86 fusion positive and 25 fusion negative). The NGS assay results were confirmed by RT-PCR and FISH tests. The overall accuracy of the NGS assay was 95.5% (106/111). No targeted gene fusions were detected in 20 negative control samples (100% specificity).

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

1. Jia Y, Xie Z, Li H: Intergenically Spliced Chimeric RNAs in Cancer. Trends Cancer 2016;2:475-482. doi: 10.1016/j.trecan.2016.07.006

2. Jo VY, Fletcher CD: WHO classification of soft tissue tumours: an update based on the 2013 (fourth) edition. Pathology 2014;46:95-104. doi: 10.1097/PAT.0000000000000050

3. Fletcher CD: The evolving classification of soft tissue tumours - an update based on the new 2013 WHO classification. Histopathology 2014;64:2-11. doi: 10.1111/his.12267

4. Quesada J, Amato R: The Molecular Biology of Soft-Tissue Sarcomas and Current Trends in Therapy. Sarcoma 2012:1-15. doi: 10.1155/2012/849456

5. Podnar J, Deiderick H, Huerta G, Hunicke-Smith S: Next-Generation Sequencing RNA-Seq Library Construction. Curr Protoc Mol Biol 106:2014;unit 4.21:1-19

6. Mertens F, Tayebwa J: Evolving techniques for gene fusion detection in soft tissue tumours. Histopathology 2014;64:151-162. doi: 10.1111/his.12272

7. AI-Zaid T, Wang WL, Somaiah N, Lazar AJ: Molecular profiling of sarcomas: new vistas for precision medicine. Virchows Arch 2017;471:243-255

8. Gao Q, Liang WW, Foltz SM, et al: Driver Fusions and Their Implications in the Development and Treatment of Human Cancers. Cell Rep 2018;23:227-238. doi: 10.1016/j.celrep.2018.03.050

9. Lam SW, Cleton-Jansen AM, Cleven AHG, et al: Molecular Analysis of Gene Fusions in Bone and Soft Tissue Tumors by Anchored Multiplex PCR-Based Targeted Next-Generation Sequencing. J Mol Diagn 2018;20:653-663. doi: 10.1016/j.jmoldx.2018.05.007

10. Roy A, Kumar V, Zorman B, et al: Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. Nat Commun 2015 Nov 17;6:8891. doi: 10.1038/ncomms9891

11. Marino-Enriquez A, Lauria A, Przybyl J, et al: BCOR Internal Tandem Duplication in High-grade Uterine Sarcomas. Am J Surg Pathol 2018 Mar;42(3):335-341. doi: 10.1097/PAS.0000000000000993

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