scholarly journals MDM2 Amplified Sarcomas: A Literature Review

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 496
Author(s):  
Raf Sciot
Keyword(s):  
Suppressor Gene ◽  
Negative Regulator ◽  
Low Grade ◽  
P53 Mutations ◽  
Lipomatous Tumor ◽  
Double Minute ◽  
Genetic Features ◽  
Murine Double Minute ◽  
Well Differentiated ◽  
Mdm2 Amplification

Murine Double Minute Clone 2, located at 12q15, is an oncogene that codes for an oncoprotein of which the association with p53 was discovered 30 years ago. The most important function of MDM2 is to control p53 activity; it is in fact the best documented negative regulator of p53. Mutations of the tumor suppressor gene p53 represent the most frequent genetic change in human cancers. By overexpressing MDM2, cancer cells have another means to block p53. The sarcomas in which MDM2 amplification is a hallmark are well-differentiated liposarcoma/atypical lipomatous tumor, dedifferentiated liposarcoma, intimal sarcoma, and low-grade osteosarcoma. The purpose of this review is to summarize the typical clinical, histopathological, immunohistochemical, and genetic features of these tumors.

Application of Molecular Biology to Individualize Therapy for Patients with Liposarcoma

2015 ◽  
pp. 213-218 ◽  
Author(s):  
Gulam Abbas Manji ◽  
Samuel Singer ◽  
Andrew Koff ◽  
Gary K. Schwartz
Keyword(s):  
Retrospective Studies ◽  
Soft Tissue Sarcomas ◽  
Definitive Treatment ◽  
Cyclin Dependent Kinase ◽  
Round Cell ◽  
Lipomatous Tumor ◽  
Appropriate Treatment ◽  
Double Minute ◽  
Murine Double Minute ◽  
Well Differentiated

Liposarcomas are one the most common of over 50 histologic subtypes of soft tissue sarcomas that are mostly resistant to chemotherapy. Histologically, liposarcomas themselves are heterogeneous and fall into four distinct subtypes: well-differentiated/atypical lipomatous tumor, dedifferentiated liposarcoma, myxoid (round cell) liposarcoma, and pleomorphic liposarcoma. Surgical resection with negative margins remains the mainstay for definitive treatment for operable disease. For unresectable disease, retrospective studies have identified myxoid (round cell) and pleomorphic sarcomas to be relatively responsive to chemotherapy. Recent studies have identified distinct genetic aberrations that not only aid in the diagnosis of particular liposarcoma subtypes, but represent actionable targets as they are considered central to disease pathogenesis. Cyclin-dependent kinase 4 (CDK4) and murine double minute 2 (MDM2) are overexpressed in well-differentiated and dedifferentiated liposarcomas and offer tantalizing opportunities that are being pursued in clinical trials. Myxoid (round cell) liposarcomas appear to be sensitive to trabectedin, which is currently under U.S. Food and Drug Administration (FDA) review. Liposarcomas do not represent a uniform disease and understanding the underlying molecular mechanism will help not only in accurate diagnosis but in selecting the appropriate treatment.

scholarly journals A rare case of atypical/anaplastic meningioma with MDM2 amplification

Rare Tumors ◽  
2018 ◽  
Vol 10 ◽  
pp. 203636131877951
Author(s):  
Robbert Wylleman ◽  
Maria Debiec-Rychter ◽  
Raf Sciot
Keyword(s):  
Rare Case ◽  
Array Comparative Genomic Hybridization ◽  
Comparative Genomic ◽  
Anaplastic Meningioma ◽  
Double Minute ◽  
Similar Report ◽  
Murine Double Minute ◽  
The Right ◽  
Mdm2 Amplification

We report the exceptional occurrence of murine double minute clone 2 amplification in an atypical meningioma and its recurrent anaplastic meningioma arising in the right frontal lobe of a 75-year-old man. Murine double minute clone 2 amplification was shown by array comparative genomic hybridization and confirmed by fluorescence in situ hybridization. This is a rare finding with only one similar report in the literature. Awareness of this finding is indicated and should not lead to misdiagnosis of other entities that more commonly show this feature.

Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma With Features Mimicking Spindle Cell Lipoma

2019 ◽  
Vol 28 (3) ◽  
pp. 336-340 ◽  
Author(s):  
Judith A. S. Jebastin ◽  
Kyle D. Perry ◽  
Dhananjay A. Chitale ◽  
Michael P. Mott ◽  
Jessica Sanchez ◽  
...  
Keyword(s):  
Spindle Cell ◽  
Spindle Cell Lipoma ◽  
Rb1 Gene ◽  
Prognostic Features ◽  
Atypical Lipomatous Tumor ◽  
Lipomatous Tumor ◽  
Well Differentiated ◽  
Mdm2 Amplification ◽  
Lipomatous Tumors

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and spindle cell lipoma are lipomatous tumors with distinct clinical, molecular, and prognostic features. Although histological and immunophenotypic features can overlap between ALT/WDL and spindle cell lipoma, the oncogenesis and clinical behavior are markedly different. In borderline cases, molecular analysis for MDM2 or CDK4 amplification can aid in distinguishing ALT/WDL from spindle cell lipoma. Although dedifferentiated liposarcoma has been reported to harbor both MDM2 amplification and loss of the RB1 region, we are not aware of a reported RB1 loss in well-differentiated ALT/WDL. In this article, we present a 69-year-old woman with a lipomatous tumor in the gluteal region that histologically, immunohistochemically, and molecularly mimicked spindle cell lipoma (with positive immunohistochemical staining for CD34 and loss of the RB1 gene region), yet harbored amplification of MDM2 and CDK4 confirmed by fluorescence in situ hybridization, supporting classification as ALT/WDL. This case strengthens the argument that in atypical clinical contexts, molecular studies for MDM2/CDK4 should be considered in tumors resembling spindle cell lipoma.

Primary well-differentiated liposarcoma of the eyelid clinically masquerading as a benign tumour: a rare entity confirmed by murine double minute 2 fluorescencein-situhybridization

2015 ◽  
Vol 67 (4) ◽  
pp. 582-585
Author(s):  
Manish M Subramaniam ◽  
Alvin Lim Soon Tiong ◽  
Lim Tse Hui ◽  
Victor Lee Kwan Min ◽  
Shantha Amrith ◽  
...  
Keyword(s):  
Benign Tumour ◽  
Rare Entity ◽  
Double Minute ◽  
Murine Double Minute ◽  
Well Differentiated

Resistance acquisition to MDM2 inhibitors

2014 ◽  
Vol 42 (4) ◽  
pp. 752-757 ◽  
Author(s):  
Jindrich Cinatl ◽  
Daniel Speidel ◽  
Ian Hardcastle ◽  
Martin Michaelis
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Small Molecule ◽  
P53 Mutations ◽  
Experimental Systems ◽  
Anti Cancer ◽  
Double Minute ◽  
Murine Double Minute ◽  
Experimental Strategies

Various experimental strategies aim to (re)activate p53 signalling in cancer cells. The most advanced clinically are small-molecule inhibitors of the autoregulatory interaction between p53 and MDM2 (murine double minute 2). Different MDM2 inhibitors are currently under investigation in clinical trials. As for other targeted anti-cancer therapy approaches, relatively rapid resistance acquisition may limit the clinical efficacy of MDM2 inhibitors. In particular, MDM2 inhibitors were shown to induce p53 mutations in experimental systems. In the present article, we summarize what is known about MDM2 inhibitors as anti-cancer drugs with a focus on the acquisition of resistance to these compounds.

PALMAR WELL DIFFERENTIATED SPINDLE CELL LIPOSARCOMA: PRESENTATION OF A RARE TUMOR AT A RARE SITE

Hand Surgery ◽  
2013 ◽  
Vol 18 (01) ◽  
pp. 115-120 ◽  
Author(s):  
Sanjay D. Deshmukh ◽  
Harveen K. Gulati ◽  
Prashant Yadav ◽  
Pooja Naik
Keyword(s):  
World Literature ◽  
Spindle Cell ◽  
Soft Tissue Sarcomas ◽  
Low Grade ◽  
Aggressive Approach ◽  
Lipomatous Tumor ◽  
Synovial Sarcomas ◽  
Rare Site ◽  
Aggressive Tumors ◽  
Well Differentiated

The most common soft tissue sarcomas of hand are epitheloid sarcomas, synovial sarcomas and malignant fibrous histiocytomas which are high grade, aggressive tumors. Liposarcomas of the hand are extremely rare and to the best of our knowledge less than 20 cases have been reported so far in the literature. Well differentiated spindle cell liposarcoma is an extremely rare subtype of well differentiated liposarcoma/atypical lipomatous tumor which is different from the other subtypes clinicopathologically, genetically and prognostically. Palmar localization of this rare variant of liposarcoma at this site makes ours only the second case reported in the world literature so far. This recently described entity is low grade lesion and the hand surgeons need to adopt a less aggressive approach in the treatment of this subtype.

“Fat-Rich” (Spindle Cell-Poor) Variant of Atypical Spindle Cell/Pleomorphic Lipomatous Tumor: Striking Mimic of “Classical” Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma

2019 ◽  
Vol 27 (8) ◽  
pp. 868-871 ◽  
Author(s):  
David Creytens ◽  
Thomas Mentzel ◽  
Liesbeth Ferdinande ◽  
Joost van Gorp ◽  
Jo Van Dorpe ◽  
...  
Keyword(s):  
Spindle Cell ◽  
Molecular Genetic ◽  
Low Grade ◽  
Tissue Mass ◽  
Atypical Lipomatous Tumor ◽  
Lipomatous Tumor ◽  
Multinucleated Cells ◽  
Pericytic Mimicry ◽  
Well Differentiated ◽  
The Right

We report the case of a “fat-rich” (spindle cell-poor) variant of an atypical spindle cell/pleomorphic lipomatous tumor in a 63-year-old female patient presenting with a firm, painless soft tissue mass on the right hip. Atypical spindle cell/pleomorphic lipomatous tumor is a very recently described low-grade adipocytic neoplasm, which occurs predominantly in adults with a predilection for the limbs and limb girdles. In the present case, the diagnosis of an atypical spindle cell/pleomorphic lipomatous tumor was challenging because the tumor was almost exclusively composed of an atypical adipocytic component (resembling “classical” atypical lipomatous tumor/well-differentiated tumor) with only very focal presence of the diagnostic atypical morphologic features (atypical spindle-shaped cells, floret-like multinucleated cells, and “bizarre” pleomorphic [multinucleated] cells). The possibility of a “classical” atypical lipomatous tumor/well-differentiated liposarcoma was ruled out by immunohistochemistry (lack of MDM2 expression and loss of Rb expression) and molecular genetic testing (no amplification of MDM2 and presence of monoallelic deletion of RB1). Another interesting morphologic observation in this case was the striking perivascular location of the atypical spindle/pleomorphic cells in some areas (so-called “pericytic mimicry”). To our knowledge, pericytic mimicry has not been reported in the setting of an atypical spindle cell/pleomorphic lipomatous tumor.

PI3K/Akt-mediated regulation of p53 in cancer

2014 ◽  
Vol 42 (4) ◽  
pp. 798-803 ◽  
Author(s):  
Aswin G. Abraham ◽  
Eric O’Neill
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Cells ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Negative Control ◽  
Double Minute ◽  
Murine Double Minute ◽  
Phosphoinositide 3 Kinase ◽  
Phosphatase And Tensin Homologue

Mutations activating the PI3K (phosphoinositide 3-kinase)/Akt signalling pathway and inactivating the TP53 tumour-suppressor gene are common mechanisms that cancer cells require to proliferate and escape pre-programmed cell death. In a well-described mechanism, Akt mediates negative control of p53 levels through enhancing MDM2 (murine double minute 2)-mediated targeting of p53 for degradation. Accumulating evidence is beginning to suggest that, in certain circumstances, PTEN (phosphatase and tensin homologue deleted on chromosome 10)/PI3K/Akt also promotes p53 translation and protein stability, suggesting that additional mechanisms may be involved in the Akt-mediated regulation of p53 in tumours. In the present article, we discuss these aspects in the light of clinical PI3K/Akt inhibitors, where information regarding the effect on p53 activity will be a crucial factor that will undoubtedly influence therapeutic efficacy.

Low-grade Osteosarcomatous Dedifferentiation of an Atypical Lipomatous Tumor in a Pediatric Patient

2019 ◽  
Vol 23 (3) ◽  
pp. 240-246
Author(s):  
Benjamin J Kukull ◽  
Mazdak A Khalighi ◽  
Kenneth R Gundle ◽  
Barry G Hansford ◽  
Christopher L Corless ◽  
...  
Keyword(s):  
Pediatric Patient ◽  
Unusual Case ◽  
Pediatric Population ◽  
Low Grade ◽  
Parosteal Osteosarcoma ◽  
Atypical Lipomatous Tumor ◽  
Lipomatous Tumor ◽  
Well Differentiated ◽  
Single Focus ◽  
Shared Characteristic

Atypical and malignant lipomatous tumors are infrequent in the pediatric population. Within this uncommon cohort, the morphologically and genetically related spectrum of atypical lipomatous tumor/well-differentiated liposarcoma/dedifferentiated liposarcoma (ALT/WDL/DDLS) is markedly rare. Their shared characteristic molecular aberration is a genomic amplicon of a region of chromosome 12q, including the oncogenes MDM2 and CDK4. We present an unusual case of a pediatric patient with an ALT, with recurrence after 2 years in the form of a bone-forming mass, radiologically and pathologically mimicking parosteal osteosarcoma, a tumor also molecularly characterized by amplification of MDM2 and CDK4. However, with ample histologic sampling, a single focus of lipogenic differentiation was identified, thus representing the first near complete low-grade osteosarcomatous dedififferentation reported within ALT/WDL/DDLS and the first ever in pediatric patient. The case serves a reminder of a diagnosis differential and pitfalls within MDM2-amplified tumors.

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