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 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.

scholarly journals Managing Liposarcomas: Cutting Through the Fat

2016 ◽  
Vol 12 (3) ◽  
pp. 221-227 ◽  
Author(s):  
Gulam A. Manji ◽  
Gary K. Schwartz
Keyword(s):  
Treatment Plan ◽  
Soft Tissue Sarcomas ◽  
Definitive Treatment ◽  
Round Cell ◽  
Myxoid Liposarcomas ◽  
Well Differentiated ◽  
Third Line ◽  
Line Setting ◽  
Pleomorphic Liposarcomas ◽  
Histologic Subtypes

Liposarcomas are one of the most common of more than 50 histologic subtypes of soft tissue sarcomas that, themselves, are heterogeneous. Liposarcomas fall into four distinct histologic subtypes: atypical lipomatous tumor/well-differentiated liposarcoma, dedifferentiated liposarcoma, myxoid (round cell) liposarcoma, and pleomorphic liposarcoma. Definitive treatment remains surgical resection with negative margins for resectable disease. However, well-differentiated liposarcomas that are large or difficult to operate upon should be followed with close surveillance as long as there is no radiologic concern for a dedifferentiated component. In contrast, first-line chemotherapy with anthracycline with or without ifosfamide, or gemcitabine and docetaxel should be used for inoperable myxoid (round cell) or pleomorphic liposarcomas, which are relatively responsive to chemotherapy. In the second- and third-line setting, myxoid liposarcomas, in particular, seem to be sensitive to trabectedin, which was recently approved by the US Food and Drug Administration (FDA). Eribulin offered a survival benefit when compared with dacarbazine in the third-line setting in liposarcomas (other than the well-differentiated subtype) and is now FDA approved. Recent studies have identified distinct genetic aberrations that not only aid in the diagnosis of liposarcoma subtypes but represent actionable targets. Cyclin-dependent kinase 4 and murine double minute 2 are overexpressed in well-differentiated and dedifferentiated liposarcomas and offer opportunities that are being pursued in clinical trials. It is critical that liposarcomas are not approached by oncologists as one disease entity but rather subclassified into distinct subtypes using histologic and molecular tools before formalizing a treatment plan.

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

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.

Cyclin-dependent kinase inhibitor 2A (p16) distinguishes well-differentiated liposarcoma from lipoma

2013 ◽  
Vol 62 (7) ◽  
pp. 1109-1111 ◽  
Author(s):  
Raul S Gonzalez ◽  
Colt M McClain ◽  
Ben K Chamberlain ◽  
Cheryl M Coffin ◽  
Justin M M Cates
Keyword(s):  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Well Differentiated

scholarly journals Biology and Management of Dedifferentiated Liposarcoma: State of the Art and Perspectives

2021 ◽  
Vol 10 (15) ◽  
pp. 3230
Author(s):  
Jun Nishio ◽  
Shizuhide Nakayama ◽  
Kazuki Nabeshima ◽  
Takuaki Yamamoto
Keyword(s):  
Standard Treatment ◽  
Clinical Presentation ◽  
Current Knowledge ◽  
Single Agent ◽  
Dedifferentiated Liposarcoma ◽  
Cyclin Dependent Kinase ◽  
First Line ◽  
First Line Therapy ◽  
Well Differentiated ◽  
Genetic Events

Dedifferentiated liposarcoma (DDL) is defined as the transition from well-differentiated liposarcoma (WDL)/atypical lipomatous tumor (ALT) to non-lipogenic sarcoma, which arises mostly in the retroperitoneum and deep soft tissue of proximal extremities. It is characterized by a supernumerary ring and giant marker chromosomes, both of which contain amplified sequences of 12q13-15 including murinedouble minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) cell cycle oncogenes. Detection of MDM2 (and/or CDK4) amplification serves to distinguish DDL from other undifferentiated sarcomas. Recently, CTDSP1/2-DNM3OS fusion genes have been identified in a subset of DDL. However, the genetic events associated with dedifferentiation of WDL/ALT remain to be clarified. The standard treatment for localized DDL is surgery, with or without radiotherapy. In advanced disease, the standard first-line therapy is an anthracycline-based regimen, with either single-agent anthracycline or anthracycline in combination with the alkylating agent ifosfamide. Unfortunately, this regimen has not necessarily led to a satisfactory clinical outcome. Recent advances in the understanding of the pathogenesis of DDL may allow for the development of more-effective innovative therapeutic strategies. This review provides an overview of the current knowledge on the clinical presentation, pathogenesis, histopathology and treatment of DDL.

Translocations and Amplifications of Chromosome 12 in Liposarcoma Demonstrated by the LSI CHOP Breakapart Rearrangement Probe

2008 ◽  
Vol 132 (6) ◽  
pp. 952-957
Author(s):  
Carlynn Willmore-Payne ◽  
Joseph Holden ◽  
Kristi C. Turner ◽  
Alan Proia ◽  
Lester J. Layfield
Keyword(s):  
Signal Amplification ◽  
Myxoid Liposarcoma ◽  
Chromosome 12 ◽  
Round Cell ◽  
High Background ◽  
Molecular Abnormalities ◽  
Not Otherwise Specified ◽  
Myxoid Liposarcomas ◽  
Well Differentiated ◽  
Atypical Lipomatous Tumors

Abstract Context.—Liposarcomas display a number of molecular abnormalities involving chromosome 12. Myxoid and round cell liposarcomas are characterized by t(12;16)(q13; p11) or t(12;22)(q13;q12) translocations. Amplifications occur within the 12q13-15 region of atypical lipomatous tumors and well-differentiated liposarcomas but not lipomas. Objective.—To investigate the performance characteristics of the LSI CHOP Breakapart Rearrangement Probe for the diagnosis of myxoid/round cell liposarcomas and atypical lipomas/well-differentiated liposarcomas. Design.—We investigated a series of lipomatous neoplasms (5 lipomas, 5 well-differentiated liposarcomas, 22 myxoid/round cell liposarcomas, 2 liposarcomas not otherwise specified, and 2 dedifferentiated liposarcomas) and normal myometrium for abnormalities in the q13-15 region of chromosome 12. Cases were studied for the presence or absence of t(12;16)(q13;p11) or t(12;22)(q13;q12) translocations by the LSI CHOP Breakapart Rearrangement Probe. These probes contain a sequence encompassing the SAS and CDK4 genes. Four or more copies of this sequence were considered to represent amplification of these genes. Results.—Rearrangement of the CHOP gene was seen in all evaluable myxoid liposarcomas. Rearrangements were seen in 1 dedifferentiated liposarcoma but not in normal myometrium or lipomas. Probe signal amplification was seen in all 5 well-differentiated liposarcomas and 1 myxoid liposarcoma. No signal amplification was seen in lipomas or myometrium. Conclusions.—Demonstration of translocations t(12; 16)(q13;p11) and t(12;22)(q13;q12) by the LSI CHOP Breakapart Rearrangement Probe appears to correlate with round cell/myxoid liposarcoma. The probe also demonstrated amplification of the 12q13-15 region in well-differentiated liposarcomas, making it useful for the diagnosis of these neoplasms. In a significant percentage of cases, high background fluorescence or poor probe staining made interpretation difficult.

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