Correlation of Classic and Molecular Cytogenetic Alterations in Soft-Tissue Sarcomas: Analysis of 46 Tumors With Emphasis on Adipocytic Tumors and Synovial Sarcoma

Rao, Uma; Cieply, Kathleen; Sherer, Carol; Surti, Urvashi; Gollin, Susanne M.

doi:10.1097/pai.0000000000000294

Cited by 14 publications

(10 citation statements)

References 31 publications

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“…Interestingly, DDIT3 gene amplification by FISH was also detected in our case. DDIT3 gene is located on 12q13.2, a region very proximate to the MDM2 and CDK4 genes [18,19]. Due to this geographic proximity, DDIT3 gene can be amplified in a subset of cases of WDL and dedifferentiated liposarcoma.…”

Section: Discussionmentioning

confidence: 99%

“…Due to this geographic proximity, DDIT3 gene can be amplified in a subset of cases of WDL and dedifferentiated liposarcoma. DDIT3 encodes for a nuclear protein in the CCAAT/enhancer-binding protein (C/EBP) family, and functions as a transcription factor that plays a role in adipogenesis and adipocytic differentiation [18][19][20][21]. It has been shown in some studies that DDIT3 gene amplification is associated with myxoid liposarcoma-like morphology [18,19].…”

Section: Discussionmentioning

confidence: 99%

“…DDIT3 encodes for a nuclear protein in the CCAAT/enhancer-binding protein (C/EBP) family, and functions as a transcription factor that plays a role in adipogenesis and adipocytic differentiation [18][19][20][21]. It has been shown in some studies that DDIT3 gene amplification is associated with myxoid liposarcoma-like morphology [18,19]. Mantilla et al evaluated the presence of DDIT3 amplification in 48 cases of de-differentiated liposarcoma and found that 33% of the cases had DDIT3 amplification, of those, 75% were associated with ML-like morphology [18].…”

Section: Discussionmentioning

confidence: 99%

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Well-Differentiated Liposarcoma of the Hypopharynx Exhibiting Myxoid Liposarcoma-like Morphology with MDM2 and DDIT3 Co-Amplification

Murshed

Samra

Ammar

2021

Head and Neck Pathol

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Well-differentiated liposarcoma (WDL) is one of the most common soft tissue sarcomas in adults. It has a predilection for middle-aged males and arises in deep-seated locations such as retroperitoneum, mediastinum, and spermatic cord. Its occurrence in young individuals at the hypopharyngeal region is an exceedingly rare event. Myxoid liposarcoma (ML)-like changes can seldom occur in some cases of WDL, which makes the diagnosis of WDL more challenging. Amplification of DDIT3 gene in a subset of cases of WDL has shown to be associated with such unique morphology. Herein, we present a case of a 36-year-old gentleman who presented with difficulty in breathing and swallowing for 3 months duration. CT scan of the neck revealed a lesion along the posterior wall of the hypopharynx measuring 3.5 cm. Histopathologic examination revealed a tumor composed of lobules of oval to spindle cells in a prominent myxoid stroma with delicate chicken-wire vasculature. In the vicinity, there were lobules composed of variably sized adipocytes separated by thick fibrous septa that contains atypical hyperchromatic spindle cells. By immunohistochemistry, the tumor cells in both components were immunoreactive for CDK4, but negative for MDM2. Fluorescence in-situ hybridization (FISH) confirmed the presence of MDM2 gene amplification. There was no evidence of FUS-DDIT3 gene rearrangement, however, DDIT3 gene was also amplified. The diagnosis of well-differentiated liposarcoma with prominent myxoid stroma was rendered. This is the first documentation of WDL with ML-like morphology harboring co-amplification of MDM2 and DDIT3 in the hypopharynx.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Well-Differentiated Liposarcoma of the Hypopharynx Exhibiting Myxoid Liposarcoma-like Morphology with MDM2 and DDIT3 Co-Amplification

Murshed

Samra

Ammar

2021

Head and Neck Pathol

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“…The specific chromosomal aberration in synovial sarcoma is t(X;18) translocation, which is used for diagnostic purposes (using cytogenetic or RT-PCR methods) [44]. Synovial sarcoma is characterised by relatively small genetic complexity -almost half of primary tumours do not carry chromosomal aberrations other than t(X;18), while in other cases only a small number of lesions occur [45].…”

Section: Synovial Sarcomamentioning

confidence: 99%

Molecular biology of sarcoma

et al. 2019

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Soft tissue sarcomas are a large group of heterogenous neoplasms, many of them are highly aggressive. Most of the cases are sporadic, without any well-defined pathogenetic factor. Potential risk factors are ionizing radiation, lymphatic oedema (secondary angiosarcoma of the breast), viral infections (HHV8 and Kaposi sarcoma), exposure to chemical factors (vinyl chloride and hepatic angiosarcoma). Genetic susceptibility plays a role in a minority of cases. However, mutations in TP53, ATM and ATR genes are associated with enhanced susceptibility to radiation. Li-Fraumeni syndrome (autosomal dominant TP53 mutation) predisposes to development of malignancies, one third of them are sarcomas. Genetic alterations observed in sarcomas could be divided into three major groups characterized by: (1) chromosome translocations; (2) simple karyotype and mutations; (3) variably complex karyotypes. A large part of sarcomas belong to the first group and the specific chromosal translocations could be utilized in the diagnostic process. A smaller number of sarcomas could be assigned to the second group, e.g. desmoid fibromatosis (CTNNB1 or APC mutations) and GIST (KIT, PDGFRA, or less frequently BRAF, SDH, NF1). A large number of sarcomas are characterized by complex and variable karyotypes. Gene copy number alterations are frequent in this group, e.g. in well-differentiated liposarcoma there is an amplification of MDM2, CDK4 and HMGA2 genes or sarcoma-specific chromosomal break regions present in the CHOP gene in myxoid liposarcoma and FKHR in alveolar rhabdomyosarcoma.

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“…The resulting protein functions as a transcriptional activator of downstream genes. This translocation can be detected by FISH and RT-PCR with high specificity and sensitivity 27, 28…”

Section: Orbital Mesenchymal Tumours Where Cytogenetics Is Useful Formentioning

confidence: 99%

An update on mesenchymal tumours of the orbit with an emphasis on the value of molecular/cytogenetic testing

Roberts

MacDuff

2018

Saudi Journal of Ophthalmology

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Mesenchymal tumours of the orbit are uncommon. Beyond childhood primary sarcomas are extremely rare and the literature is limited to case reports and short case series. However there is a diverse assortment of benign and malignant soft tissue tumours that may involve the orbit. Techniques to identify tumour specific cytogenetic or molecular genetic abnormalities often resulting in over- expressed proteins are becoming an increasingly important ancillary technique for these tumours. This review focuses on 3 specific areas: 1. Orbital mesenchymal tumours where cytogenetics are important to reach the correct diagnosis. The majority of these are chromosomal translocations that often result in a fusion gene and protein product; 2. Orbital mesenchymal tumours where cytogenetics are important to identify patients who will do well versus those with a poorer prognosis. This is turn helps with therapeutic options. In some tumours e.g. synovial sarcoma the chromosomal translocations can occur with 2 different regions resulting in different fusion products that carry a different prognosis. Alternatively whilst the majority of alveolar rhadomyosarcomas are fusion positive a minority are fusion negative with a better prognosis; 3. Orbital mesenchymal tumours where the identification of specific cytogenetic abnormalities has resulted in overexpression of specfic proteins which are diagnostically useful biomarkers for immunohistochemistry.

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Correlation of Classic and Molecular Cytogenetic Alterations in Soft-Tissue Sarcomas: Analysis of 46 Tumors With Emphasis on Adipocytic Tumors and Synovial Sarcoma

Cited by 14 publications

References 31 publications

Well-Differentiated Liposarcoma of the Hypopharynx Exhibiting Myxoid Liposarcoma-like Morphology with MDM2 and DDIT3 Co-Amplification

Well-Differentiated Liposarcoma of the Hypopharynx Exhibiting Myxoid Liposarcoma-like Morphology with MDM2 and DDIT3 Co-Amplification

Molecular biology of sarcoma

An update on mesenchymal tumours of the orbit with an emphasis on the value of molecular/cytogenetic testing

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