p14ARF methylation is a common event in the pathogenesis and progression of myxoid and pleomorphic liposarcoma

Davidović, Radoslav; Sopta, Jelena; Mandušić, Vesna; Krajnović, Milena; Stanojević, Maja; Tulic, Goran; Dimitrijević, Bogomir

doi:10.1007/s12032-013-0682-9

Cited by 13 publications

(13 citation statements)

References 26 publications

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“…11 Loss of the tumor suppressor gene NF1 is exhibited in a proportion of patients, whereas epigenetic silencing of the p53 target gene p14ARF has been implicated as playing a role in tumorigenesis. 12,28…”

Section: Lps Subtypesmentioning

confidence: 99%

Clinical and Molecular Spectrum of Liposarcoma

Lee

Thway

Huang

et al. 2018

JCO

248

245

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Liposarcomas are rare malignant tumors of adipocytic differentiation. The classification of liposarcomas into four principal subtypes reflects the distinct clinical behavior, treatment sensitivity, and underlying biology encompassed by these diseases. Increasingly, clinical management decisions and the development of investigational therapeutics are informed by an improved understanding of subtype-specific molecular pathology. Well-differentiated liposarcoma is the most common subtype and is associated with indolent behavior, local recurrence, and insensitivity to radiotherapy and chemotherapy. Dedifferentiated liposarcoma represents focal progression of well-differentiated disease into a more aggressive, metastasizing, and fatal malignancy. Both of these subtypes are characterized by recurrent amplifications within chromosome 12, resulting in the overexpression of disease-driving genes that have been the focus of therapeutic targeting. Myxoid liposarcoma is characterized by a pathognomonic chromosomal translocation that results in an oncogenic fusion protein, whereas pleomorphic liposarcoma is a karyotypically complex and especially poor-prognosis subtype that accounts for less than 10% of liposarcoma diagnoses. A range of novel pharmaceutical agents that aim to target liposarcoma-specific biology are under active investigation and offer hope of adding to the limited available treatment options for recurrent or inoperable disease.

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Section: Lps Subtypesmentioning

confidence: 99%

Clinical and Molecular Spectrum of Liposarcoma

Lee

Thway

Huang

et al. 2018

JCO

248

245

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“… 41 Recent studies have hypothesized the role of p14 ARF methylation in the origin and growth of PLS. 42 …”

Section: Histopathology and Clinical Behaviormentioning

confidence: 99%

Current classification, treatment options, and new perspectives in the management of adipocytic sarcomas

Vita

Mercatali

Recine

et al. 2016

OTT

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Sarcomas are a heterogeneous group of mesenchymal tumors arising from soft tissue or bone, with an uncertain etiology and difficult classification. Soft tissue sarcomas (STSs) account for around 1% of all adult cancers. Till date, more than 50 histologic subtypes have been identified. Adipocyte sarcoma or liposarcoma (LPS) is one of the most common STS subtypes, accounting for 15% of all sarcomas, with an incidence of 24% of all extremity STSs and 45% of all retroperitoneal STSs. The new World Health Organization classification system has divided LPS into four different subgroups: atypical lipomatous tumor/well-differentiated LPS, dedifferentiated LPS, myxoid LPS, and pleomorphic LPS. These lesions can develop at any location and exhibit different aggressive potentials reflecting their morphologic diversity and clinical behavior. Patients affected by LPS should be managed in specialized multidisciplinary cancer centers. Whereas surgical resection is the mainstay of treatment for localized disease, the benefits of adjuvant and neoadjuvant chemotherapy are still unclear. Systemic treatment, particularly chemotherapy, is still limited in metastatic disease. Despite the efforts toward a better understanding of the biology of LPS, the outcome of advanced and metastatic patients remains poor. The advent of targeted therapies may lead to an improvement of treatment options and clinical outcomes. A larger patient enrollment into translational and clinical studies will help increase the knowledge of the biological behavior of LPSs, test new drugs, and introduce new methodological studies, that is, on treatment response.

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“…There have been limited studies investigating the epigenetics of myxoid LPS [11,[42][43][44] . Epigenetic silencing of p14ARF, a p53 target, by promoter methylation has been reported as a common event in both myxoid and pleomorphic LPS.…”

Section: Epigenetic Alterationsmentioning

confidence: 99%

“…There is not much known about the epigenetics of pleomorphic LPS [11,42] . As noted before, promoter methylation resulting in epigenetic silencing of p14ARF has been reported as a common event in both myxoid and pleomorphic LPS.…”

Section: Epigenetic Alterationsmentioning

confidence: 99%

Overview of liposarcomas and their genomic landscape

Keung¹,

Somaiah²

2019

JTGG

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Liposarcoma (LPS) is among the most common soft tissue sarcoma affecting adults. LPS is divided into three biologic subtypes characterized by specific genetic alterations. The most common LPS subtypes, well-differentiated and dedifferentiated LPS, are nearly uniformly characterized by ring chromosomes and giant markers with chromosomal amplification of 12q13-15 and resulting amplification of oncogenes MDM2 , CDK4 , and HMGA2. Myxoid/round cell LPS commonly exhibits a distinctive (12; 16) translocation resulting in the FUS-DDIT3 fusion gene. Finally, pleomorphic LPS harbors diverse complex genomic changes and chromosomal rearrangements and frequent mutations in TP53 , RB1 , and NF1 leading to dysregulation of tumor suppressor pathways. In this review, we summarize the currently available knowledge on the genomics and genetics of LPS subtypes as well as recent advances in the multimodality management of LPS.

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p14ARF methylation is a common event in the pathogenesis and progression of myxoid and pleomorphic liposarcoma

Cited by 13 publications

References 26 publications

Clinical and Molecular Spectrum of Liposarcoma

Clinical and Molecular Spectrum of Liposarcoma

Current classification, treatment options, and new perspectives in the management of adipocytic sarcomas

Overview of liposarcomas and their genomic landscape

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