Test Catalog


Molecular Diagnosis Of Bone And Soft Tissue Tumors

May 2014


Bone and soft tissue tumors are a heterogeneous group of tumors with distinct lines of differentiation and biologic behavior. Traditionally, light microscopy has been considered the gold standard for the diagnosis of these tumors. However, supportive molecular genetic methods are currently viewed as an important tool for diagnostic confirmation and therapeutic considerations in many bone and soft tissue tumors.

From the cytogenetic/molecular perspective, bone and  soft tissue tumors can be broadly divided into 2 major groups: those with complex and apparently several nonspecific cytogenetic and molecular genetic features, and those harboring relatively simple cytogenetic profiles with consistent and recurrent molecular aberrations. The second group is the major focus of this article.

Most of the molecular or molecular cytogenetic tests described are commonly employed on paraffin-embedded tissues, which make them readily applicable to most surgical pathology specimens, including core biopsies and cytology specimens. Presently, nearly all these tests are based on 2 major platforms: real-time polymerase chain reaction (PCR) and variants, and fluorescence in situ hybridization (FISH). However, traditional cytogenetic evaluation is still useful for a variety of clinical scenarios in which disease-specific tests are not currently available. In this regard, certain chromosomal abnormalities may provide guidance for further disease-specific testing or in the discrimination between malignant and benign tumors. Finally, with the advent of high-throughput sequencing and micro-array technologies, it is expected that in the near future large panels for a variety of sarcoma-related molecular abnormalities will be routinely used in  clinical practice.

Alveolar Soft Part Sarcoma

Alveolar soft part sarcoma (ASPS) is an aggressive tumor of uncertain line of differentiation that predominantly affects patients from 15 to 35 years.1 Histologically, ASPS is characterized by an epithelioid population of cells arranged in typical architecture that resembles the pulmonary parenchyma. The nonbalanced chromosomal translocation der(17)t(X;17)(p11;q25) is characteristic of ASPS and results in fusion of the glucose transporter 4-interacting protein gene ASPSCR1 (formerly ASPL) to the transcription factor gene TFE3. Two types of ASPSCR1/TFE3 fusion transcripts have been described.2ASPSCR1/TFE3 is also seen in a subset of pediatric renal cell carcinomas.3 The fusion ASPSCR1/TFE3 seems to stimulate the mesenchymal epithelial transition (MET) factor signaling pathway, which could be a potential therapeutic target for MET inhibitors.4 In fact, the multikinase inhibitor sunitinib has demonstrated clinical efficacy in the treatment of ASPS, possibly via an indirect rearranged during transfection (RET)-mediated inhibition of MET.5,6

The diagnosis of ASPS is usually made at the histologic level but immunohistochemical analysis for TFE3 protein expression or molecular cytogenetic analysis for TFE3 rearrangements (by FISH) can be used for diagnostic confirmation.7 Interestingly, the same test can be used for the detection of TFE3 rearrangements in renal cell carcinomas with chromosomal translocations  involving Xp11.2.

Aneurysmal Bone Cyst

Aneurysmal bone cyst (ABC) is a primary bone tumor with potential for local recurrence that predominantly affects younger patients. The lesion may also occur in association with other bone tumors (secondary ABC). Histologically, ABC is characterized by a bland spindle cell proliferation associated with hemorrhagic cysts. At the molecular level, primary ABC is characterized by the presence of USP6 fusion genes in approximately 70% of cases.8 The most common is CDH11/USP6 due to the chromosomal translocation t(16;17). These abnormalities are not seen in secondary ABC.

The diagnosis of ABC is usually made at the histologic level, but FISH for rearrangements of the USP6 locus may support the diagnosis of primary ABC in challenging cases. The test is also useful for the diagnosis of nodular fasciitis.

Nodular Fasciitis

Nodular fasciitis (NF) is a relatively common benign and self-limited spindle cell proliferation that usually occurs  in the upper extremities and trunk of younger patients.  The clinical relevance of the lesion resides in the fact that it is commonly confused with sarcomas, especially by  the nonspecialist. Most examples of NF are characterized by USP6 fusion genes, more commonly the fusion of the nonmuscular myosin MYH9 to the ubiquitin  protease USP6.9

FISH for rearrangements of the USP6 locus in NF is highly sensitive and specific for the diagnosis of NF in the appropriate clinical context.

Angiomatoid Fibrous Histiocytoma

Angiomatoid fibrous histiocytoma (AFH) is a rare subcutaneous tumor of “histiocytoid” morphology and uncertain line of differentiation that arises predominantly in the extremities of young patients. AFH may occasionally recur, but has very limited metastatic potential. Despite the name, it is important to notice that AFH shows no clinico-biologic relationship to high-grade pleomorphic sarcomas (previously known as malignant fibrous histiocytoma or MFH). Most AFH harbor the fusion gene EWSR1/CREB1 due to the chromosomal t(2;22)(q33;q12). However, other fusion genes have been described, including EWSR1/ATF1 and FUS/ATF1.

FISH for the detection of EWSR1 rearrangements can be used to confirm the diagnosis of AFH.10 If these are negative, a possible rearrangement of the FUS locus may be considered.

Clear Cell Sarcoma of Soft Tissue

Clear cell sarcoma of soft tissue (CCS) is a rare soft tissue neoplasm that predominantly occurs in the distal extremities of adolescents and young adults. Histologically, it is characterized by an epithelioid to spindle cell population with clear cytoplasm.11 Cytogenetically, clear cell sarcoma is characterized by the t(12;22)(q13;q12) in almost all cases, which results in fusion of EWSR1 to transcriptional factor ATF1.12 This same fusion gene is also present in a subset of AFH and in hyalinizing clear cell carcinomas of the salivary gland.13,14 At least 4 major EWSR1/ATF1 splicing variants have been described.15

A common dilemma in diagnostic pathology is the differentiation of CCS from melanoma. In this regard, the identification of rearrangements of the EWSR1 locus by FISH supports the diagnosis of CCS.

Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans (DFSP) is a highly infiltrative low-grade superficial spindle cell sarcoma that shows a high local recurrence rate. Occasionally, histologic transformation into a high-grade sarcoma (fibrosarcomatous DFSP) is observed, increasing the risk of distant metastasis.16,17 Cytogenetically, DFSP and its pediatric counterpart–giant cell fibroblastoma (GCF)–are characterized by supernumerary ring chromosomes derived from chromosome 22 (predominantly DFSP), or by the presence of the reciprocal translocation t(17;22) (predominantly GCF).18 At the molecular level, both cytogenetic abnormalities result in the fusion of COL1A1 on chromosome 17q to PDGFB on chromosome 22q.19 The COL1A1/PDGFB fusion activates the PDGFRB tyrosine kinase signaling pathway, which renders DFSP responsive to tyrosine kinase inhibitors, such as imatinib mesylate.20

Molecular cytogenetic analysis (FISH) for rearrangements  of the PDGFB locus is commonly used to differentiate DFSP from other superficial low-grade sarcomas.  The test is highly sensitive and specific and provides therapeutic information.

Desmoid-Type Fibromatosis

Desmoid-type fibromatosis (DTF) is a locally aggressive fibroblastic/myofibroblastic tumor devoid of metastatic potential, and a subset of cases is associated with familial adenomatous polyposis. The most characteristic genetic event in DTF with diagnostic significance is the presence of activating mutations in CTNNB1, the gene that encodes beta-catenin. The mutations occur more commonly at codons 41 and 45 on exon 3.21 Greater than 80% of sporadic DTF harbor these mutations.22,23

The identification of beta-catenin mutations by pyrosequencing analysis is more sensitive and specific than immunohistochemical analysis, and can be used clinically to differentiate DTF from reactive fibrous tissue and other mesenchymal tumors, especially in small biopsy samples.

Desmoplastic Small Round Cell Tumor

Desmoplastic small round cell tumor (DSRCT) is a rare and highly malignant small round cell tumor with polyphenotypic differentiation and poor prognosis that tends to occur in the abdominal cavity of male adolescents and young adults. The characteristic phenotype is the coexpression of cytokeratins and desmin. Nearly 100% of DSRCTs are characterized by the chromosomal translocation t(11;22)(p13;q12), which results in the fusion of EWSR1 to the Wilms tumor suppressor gene (WT1).24 While WT1 is a classical tumor suppressor gene, the fusion protein behaves as an oncogene.

EWSR1/WT1 fusion is commonly detected using PCR, which is a highly specific and sensitive test.25

Epithelioid Sarcoma

Epithelioid sarcoma is a rare sarcoma of uncertain line of differentiation that predominantly occurs in the distal extremities of adolescents and young adults.26 At the molecular level, epithelioid sarcoma is characterized by inactivating mutations or deletions of the tumor suppressor gene SMARCB1 (INI1).27

No molecular tests are currently available for detecting inactivating mutations of SMARCB1. However, the identification of INI1 loss at the protein level by immunohistochemistry is a sensitive and specific test for supporting the diagnosis of epithelioid sarcoma or tumors with inactivating mutations of SMARCB1 (eg atypical teratoid-rhabdoid tumor).

Ewing Sarcoma

Ewing sarcoma (ES) is a small round cell neoplasm of neuroectodermal differentiation that more commonly arises in bone and soft tissues of adolescents and children.28  ES was the first sarcoma to be associated with a recurrent chromosomal translocation.29 The most common is the chromosomal translocation t(11;22)(q24;q12), which results in the fusion transcript EWSR1 to the ETS transcriptional factor FLI1.30 Several other fusion genes have been identified in ES, though EWSR1/FLI1 (90%) and ERG  (3%-5%) are by far the most common. Rare ES cases harbor the FUS/ERG fusion due to the translocation t(16;21).31 More recently, other small round cell tumors with an Ewing sarcoma-like morphology have been described, including an aggressive group characterized by the fusion gene CIC/DUX432 and another harboring BCOR/CCNB3.33

Different approaches can be used to confirm the diagnosis of ES at the molecular level. PCR for the 2 most common fusion genes EWSR1/FLI1 and EWSR1/ERG is highly sensitive and specific. If these are negative and the diagnosis of ES is still under consideration, FISH for rearrangements of EWSR1 or FUS may be considered since they can also cover rarer fusion genes. However, a few details are worth mentioning. First, rearrangements of EWSR1 or FUS are not specific for ES, so a positive FISH test is only useful when used in the context of a supportive immunophenotype. Second, a negative PCR result for EWSR1/FLI1 and EWSR1/ERG does not necessarily mean that one may be dealing with a rare ES fusion gene. Some splice variants of these common fusion genes may be missed by PCR, especially on paraffin-embedded tissues. Finally, a negative FISH result does not exclude the diagnosis of ES either since cryptic rearrangement of the EWSR1 or FUS fusion genes may be present.

Extraskeletal Myxoid Chondrosarcoma

Extraskeletal myxoid chondrosarcoma (EMC) is a rare myxoid sarcoma that, despite the name, shows an uncertain line of differentiation. The tumor often occurs in the lower extremities of older individuals and exhibits a variable clinical course. At the molecular level, approximately 75% of EMC are characterized by the fusion gene EWSR1/NR4A3 due to the chromosomal translocation t(9;22)(q22;q12).34Alternate NR4A3 gene partners have been described in occasional cases.

One of the most important differential diagnoses of EMC  is the more recently recognized soft tissue myoepithelioma, another tumor characterized by EWSR1 fusion genes.35,36 FISH for EWSR1 will not differentiate between these tumors but may be helpful in association with supportive immunohistochemical analysis since EMC and soft tissue myoepithelioma show distinct immunophenotypes.  FISH analysis for NR4A3 and the detection of specific fusion genes are tests under consideration for  further development.

Infantile Fibrosarcoma

Infantile fibrosarcoma (IFS) is a rare spindle cell neoplasm of infancy with a more favorable prognosis that is characterized by the chromosomal t(12;15)(p13;q26). This translocation results in the fusion of the transcription factor gene ETV6 (also known as TEL) to the tyrosine kinase gene NTRK3 (also known as TRKC).37 Trisomy of chromosomes 8, 11, 17, and 20 are also characteristically seen in IFS.38Interestingly, a subset of mesoblastic nephroma, a renal neoplasm of infancy, also harbors the ETV6/NTRK3 gene fusion and likely represents the same entity. This gene fusion has also been demonstrated in other tumors including secretory carcinomas of the breast, mammary analogue secretory carcinomas of the salivary gland, and a subset of acute myeloid leukemia.

FISH for rearrangements of the ETV6 locus is commonly used for diagnostic confirmation of IFS and the test is currently in development.

Inflammatory Myofibroblastic Tumor

Inflammatory myofibroblastic tumor (IMT) is a spindle cell neoplasm with myofibroblastic differentiation that often occurs in younger patients. IMT may recur locally but rarely metastasizes. The tumor is characterized by fusion genes involving the tyrosine kinase gene ALK (anaplastic lymphoma kinase) on chromosome 2p23. Several ALK fusion genes have been described but the most common areTPM3/ALK and TPM4/ALK.39 These are present in approximately 30% to 50% of cases diagnosed in patients younger than 30 years. Recently, the ALK tyrosine kinase inhibitor crizotinib has been used successfully in patients with IMT.40

Immunohistochemical analysis for ALK protein overexpression is a good first step in identifying the presence of ALK fusion proteins and the pattern of expression may even suggest the type of fusion gene involved. (Figure 1) The result can then be confirmed by FISH. Interestingly, rare examples of IMT can be weakly positive or negative for ALK, but still harbor ALK fusion genes.

Figure 1. ALK overexpression in inflammatory myofibroblastic tumor

Low-Grade Fibromyxoid Sarcoma

Low-grade fibromyxoid sarcoma (LGFMS) is a neoplasm that more commonly affects young patients and has potential for distant metastasis, often years after the initial diagnosis.41 The tumor is characterized by the translocation t(7;16)(q33;p11), which results in the fusion gene FUS/CREB3L2.42 Other fusion genes, including FUS/CREB3L and EWSR1/CREB3L1, have also been described.43,44 These gene fusions can be detected by PCR in up to  70% to 95% of cases.43,45

FISH for FUS is commonly used for diagnostic confirmation. This test can also be helpful for the diagnosis of AFH  and ES. (Figure 2)

Figure 2. Break-apart FISH for the FUS locus supports the diagnosis of low-grade fibromyxoid sarcoma and may also be used for other tumors.

Well-Differentiated Liposarcoma  and Dedifferentiated Liposarcoma

Well-differentiated liposarcoma (WDL)/atypical lipomatous tumor (ALT) is one of the most common sarcomas. WDL/ALT shows adipocytic differentiation, often recurs locally, and may occasionally transform into a high-grade dedifferentiated liposarcoma (DL). Cytogenetic studies of WDL/ALT/DL nearly universally show ring or giant marker chromosomes that consistently contain amplified sequences derived from chromosome 12q13-q15, which contains MDM2, CPM, FRS2, SAS, HMGA2, and CDK4, among other genes.46 Amplification of these genes is not specific for WDL/DL because it can also be seen in many other sarcomas and nonmesenchymal tumors.

The major diagnostic relevance in detecting these abnormalities is that they are not present in ordinary lipomas, the most important differential diagnosis for WDL/ALT. FISH for the amplification of CPM is quite helpful in the discrimination between lipomas and well-differentiated liposarcoma.47,48 (Figure 3)

Figure 3. Identification of CPM/MDM2 amplification by FISH is useful in the discrimination of well-differentiated liposarcoma from lipoma.

Mesenchymal Chondrosarcoma

Mesenchymal chondrosarcoma (MC) is a rare sarcoma that occurs more commonly in bone, but may also arise in the soft tissues. Most examples of MC are characterized by the fusion gene HEY1/NCOA2. This fusion seems to be the result of a small interstitial deletion on the long arm of chromosome 8 where both genes are located.49 More recently a t(1;5)(q42;q32) harboring the IRF2BP2/CDX1 gene fusion was described in a single case.50

PCR for HEY1/NCOA2 is currently in development as a molecular test for diagnostic confirmation of MC.

Myxoid/Round Cell Liposarcoma

Myxoid liposarcoma (ML) is the second most common type of liposarcoma and often occurs in middle-aged adults. Round cell liposarcoma (RCL) is the higher grade counterpart of ML.41 Both ML and RCL exhibit the chromosomal translocation t(12;16)(q13;p11) in as many as 90% to 95% of cases, which results in fusion of FUS to DDIT3 (also known as FUS/CHOP).51 The second most common chromosomal translocation, t(12;22)(q13;q12), occurs in a minority of patients and results in the fusion gene EWSR1/DDIT3.52

FISH for DDIT3 is commonly used to confirm the diagnosis of ML/RCL. The test is highly specific and sensitive.

Myxoinflammatory Fibroblastic Sarcoma

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare and locally recurrent sarcoma that almost always occurs in the distal extremities.41 The tumor is characterized by the chromosomal translocation t(1;10)(p22-31;q24-25) that causes the rearrangement of 2 genes: TGFBR3 and MGEA5. The translocation has also been observed in the related hemosiderotic fibrolipomatous tumor. Interestingly, no fusion gene is formed but the rearrangement leads to the overexpression of the nearby gene FGF8.53 Whether FGF8 overexpression explains the pathogenesis of MIFS remains to be determined.

A molecular cytogenetic test for MIFS is in development.

Ossifying Fibromyxoid Tumor of Soft Parts

Ossifying fibromyxoid tumor of soft parts (OFMT) is a tumor of uncertain histogenesis that, in most instances, behaves in a benign fashion. However, OFMT may recur locally or even metastasize in occasional instances. At the molecular level, OFMT is mainly characterized by PHF1 rearrangements and fusion genes.54,55

A molecular cytogenetic test for PHF1 rearrangement is currently available.

Alveolar Rhabdomyosarcoma

Alveolar rhabdomyosarcoma (ARMS) is a malignant neoplasm that exhibits skeletal muscle differentiation that often occurs in the extremities of children and adolescents.41 Histologically, the tumor is composed of nests of epithelioid-like cells. ARMS is characterized by 2 major chromosomal translocations: t(2;13)(q35;q14) and t(1;13)(p36;q14), which result in the fusion transcripts PAX3/FOXO1 and PAX7/FOXO1, respectively.56-58 These fusion genes are present in 54% to 87% and 8% to 15% of cases, respectively.56 Other less common fusion genes include PAX3/NCOA1, PAX3/AFX, and a fusion involving FOXO1/FGFR1.59-61

PCR for these fusion genes is sensitive and 100%  specific. Alternatively, FISH for rearrangements for FOXO1 can be used for diagnostic confirmation.25 Similar pitfalls  as described for ES apply to the molecular diagnosis  of ARMS.

Solitary Fibrous Tumor

Solitary fibrous tumor (SFT) is a tumor of uncertain cell of origin, originally described in the pleura but now has been recognized virtually in any site of the body. SFT behaves usually in a benign fashion but up to 10% of cases can present with local recurrences or metastasis. Recently, NAB2/STAT6 fusion gene has been identified in 90% to 100% of SFT by high-throughput transcriptome sequencing.62,63 The fact that both NAB2 and STAT6 are contiguous genes located on chromosome 12q13.3, but display opposite orientation, suggests that an inversion/deletion mechanism is involved in the fusion.63

PCR for NAB2/STAT6 is currently in development.

Synovial Sarcoma

Synovial sarcoma (SS) is a high-grade spindle cell sarcoma of uncertain line of differentiation that particularly affects adolescents and young adults.41 Cytogenetic and molecular studies demonstrate the chromosomal translocation t(X;18)(p11.2;q11.2) in most cases, resulting in the fusion of SYT with members of the SSX family of transcriptional repressor genes on chromosome Xp11.2.64 The most common fusion gene is SS18/SSX1 (65%), followed by SS18/SSX2 (35%), and rarely SS18/SSX4.65-67 While biphasic synovial sarcoma usually harbors the SS18/SSX1 fusion gene, SS18/SSX2 is associated with both morphologic subtypes. Initial studies had suggested that these fusion genes were associated with biologic behavior of SS.68 However, more recent studies have not confirmed this.69,70

PCR for the most common fusion genes and FISH for rearrangements of the SS18 locus are highly sensitive and specific and are commonly used to confirm the diagnosis of synovial sarcoma at the molecular level.25 It is important to state that there are advantages and disadvantages for each. While PCR does not detect the rare SS18/SSX4 fusion gene, which is indirectly detected with FISH, cryptic rearrangements of SS18, which are not usually detected by FISH, have been reported in occasional cases.

New Technologies

With the development of high-throughput sequencing technologies, many abnormalities described in this article will likely soon be analyzed in parallel. Furthermore, while the detection of specific fusion genes on paraffin-embedded tissues remains a challenge for routine clinical applications, especially due to certain bioinformatics constraints, it is very likely these issues will be solved in the near future.

Bone and Soft Tissue Tumor Mayo Test ID Test Name
Alveolar Soft Part Sarcoma
Alveolar Soft Part Sarcoma (ASPS)/Renal Cell Carcinoma (RCC), Xp11.23 (TFE3), FISH, Tissue
Aneurysmal Bone Cyst
USP6 (17p13), Aneurysmal Bone Cyst and Nodular Fasciitis, FISH
Nodular Fasciitis
USP6 (17p13), Aneurysmal Bone Cyst and Nodular Fasciitis, FISH
Angiomatoid Fibrous Histiocytoma
Ewing Sarcoma (EWS) 22q12 Rearrangement, FISH, Tissue
Angiomatoid Fibrous Histiocytoma
Low-Grade Fibromyxoid Sarcoma (LGFMS), 16p11 (FUS or TLS) Rearrangement, FISH, Tissue
Clear Cell Sarcoma of Soft Tissue
Ewing Sarcoma (EWS) 22q12 Rearrangement, FISH, Tissue
Dermatofibrosarcoma Protuberans
PDGFB, 22q13, for Dermatofibrosarcoma Protuberans/Giant Cell Fibroblastoma, FISH
Desmoid-Type Fibromatosis
Beta-Catenin, Fibromatosis, Mutation Analysis
Desmoplastic Small Round-Cell Tumor
Desmoplastic Small Round-Cell Tumor (DSRCT) by Reverse Transcriptase PCR (RT-PCR), Paraffin
Epithelioid Sarcoma
Integrase Interactor 1 (INI/BAF47), Immunostain
Ewing Sarcoma
Ewing Sarcoma (EWS) 22q12 Rearrangement, FISH, Tissue
Ewing Sarcoma
Ewing Sarcoma/Primitive Neuroectodermal Tumors (ES/PNET) by Reverse Transcriptase PCR (RT-PCR), Paraffin
Ewing Sarcoma
Low-Grade Fibromyxoid Sarcoma (LGFMS), 16p11 (FUS or TLS) Rearrangement, FISH, Tissue
Extraskeletal Myxoid Chondrosarcoma
Ewing Sarcoma (EWS) 22q12 Rearrangement, FISH, Tissue
Extraskeletal Myxoid Chondrosarcoma
In development
FISH analysis for NR4A3 and the detection of specific fusion genes are tests under consideration for further development.
Infantile Fibrosarcoma
In development
FISH for rearrangements of the ETV6 locus
Inflammatory Myofibroblastic Tumor
Anaplastic Lymphoma Kinase (ALK), Immunostain
Inflammatory Myofibroblastic Tumor
Inflammatory Myofibroblastic Tumors (IMT), 2p23 Rearrangement, FISH, Tissue
Low-Grade Fibromyxoid Sarcoma
Low-Grade Fibromyxoid Sarcoma (LGFMS), 16p11 (FUS or TLS) Rearrangement, FISH, Tissue
Well-Differentiated Liposarcoma
and Dedifferentiated Liposarcoma
CPM, 12q15, for Well-Differentiated Liposarcoma/Atypical Lipomatous Tumor, FISH
Mesenchymal Chondrosarcoma
In development
Myxoid/Round Cell Liposarcoma
Myxoid/Round Cell Liposarcoma 12q13 (DDIT3 or CHOP) Rearrangement, FISH, Tissue
Myxoinflammatory Fibroblastic Sarcoma
In development
A molecular cytogenetic test for MIFS is under development
Ossifying Fibromyxoid Tumor of Soft Parts
Endometrial Stromal Tumors (EST), 7p15 (JAZF1), 6p21.32 (PHF1), 17p13.3 (YWHAE) Rearrangement, FISH, Tissue
Alveolar Rhabdomyosarcoma
Alveolar Rhabdomyosarcoma (ARMS) by Reverse Transcriptase PCR (RT-PCR), Paraffin
Alveolar Rhabdomyosarcoma
Alveolar Rhabdomyosarcoma (ARMS), 13q14 (FOXO1 or FKHR) Rearrangement, FISH, Tissue
Solitary Fibrous Tumor
In development
Synovial Sarcoma
Synovial Sarcoma by Reverse Transcriptase PCR (RT-PCR), Paraffin
Synovial Sarcoma
Synovial Sarcoma (SS), 18q11.2 (SS18 or SYT) Rearrangement, FISH, Tissue
Table. Mayo Medical Laboratories Tests for Bone and Soft Tissue Tumor


The discovery of EWSR1/FLI1 fusion in Ewing sarcoma in the early 1990s represented a landmark for a series of other discoveries that took place during that decade, including the identification of the genes responsible for alveolar rhabdomyosarcoma, synovial sarcoma, and  myxoid liposarcoma.30,51,64,71 In the past decade, the completion of the human genome led to an increased pace of new discoveries. At the same time, a widespread incorporation of these new findings into the clinical molecular diagnostic practice for sarcomas took place. Currently, the recent and impressive developments in sequencing technologies are not only causing an avalanche of new discoveries in the field, they are also pushing forward the rapid implementation of these findings into routine clinical practice.

Authored by Andre M. Oliveira, MD, PhD
Mayo Clinic Muculoskeletal  Disease-Oriented Group Members:
Jorge Torres-Mora, MD
Karen Fritchie, MD 
Steven I. Robinson, MBBS
Andre M. Oliveira, MD, PhD


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