Abstract
Diagnostic histopathology of soft tissue tumors can be troublesome as many entities are quite rare and have overlapping morphologic features. Many soft tissue tumors harbor tumor‐defining gene translocations, which may provide an important ancillary tool for tumor diagnosis. The NanoString nCounter platform enables multiplex detection of pre‐defined gene fusion transcripts in formalin‐fixed and paraffin‐embedded tissue. A cohort of 104 soft tissue tumors representing 20 different histological types was analyzed for the expression of 174 unique gene fusion transcripts. A tumor‐defining gene fusion transcript was detected in 60 cases (58%). Sensitivity and specificity of the NanoString assay calculated against the result of an alternative molecular method were 85% and 100%, respectively. Highest diagnostic coverage was obtained for Ewing sarcoma, synovial sarcoma, myxoid liposarcoma, alveolar rhabdomyosarcoma, and desmoplastic small round cell tumor. For these tumor types, the NanoString assay is a rapid, cost‐effective, sensitive, and specific ancillary screening tool for molecular diagnosis. For other sarcomas, additional molecular testing may be required when a translocation transcript is not identified with the current 174 gene fusion panel.
Highlights
Soft tissue tumors represent a remarkably heterogeneous group of neoplasms, with many subtypes being exceptionally rare
A significant number of soft tissue tumors, in particular those with monomorphic round cell, spindle cell or epithelioid morphology, harbor recurrent gene translocations, which are often tumor-specific. These unique recurrent translocations were first discovered in the early 1990s by chromosomal banding techniques, for example, the t(X;18)(p11;q11) translocation in synovial sarcoma, which results in the tumor specific SS18-SSX fusion genes.[2]
In this quality control study, we evaluated the sensitivity and specificity of the NanoString nCounter platform for gene fusion detection in 22 different soft tissue tumors, adding our results to the initial report on this method.[7]
Summary
Soft tissue tumors represent a remarkably heterogeneous group of neoplasms, with many subtypes being exceptionally rare. Pathologists have witnessed the rapid development of generation sequencing (NGS) techniques, which allow simultaneous detection of multiple fusion transcripts This translated into more accurate classification and prognostication of soft tissue tumors.[3] At present, the two novel molecular multiplex methods commonly used in Dutch sarcoma centers are the anchored multiplex PCR (AMP)-based NGS (Archer FusionPlex Sarcoma assay)[4] and the NanoString nCounter platform.[5] The Archer AMP PCR method targets exons of 26 genes commonly involved in fusion genes of soft tissue tumors, whereas the NanoString assay is a high-throughput hybridization technique, which uses specific probes that target 174 unique gene fusion junctions in 22 soft tissue tumor types.[6]. In this quality control study, we evaluated the sensitivity and specificity of the NanoString nCounter platform for gene fusion detection in 22 different soft tissue tumors, adding our results to the initial report on this method.[7]
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