Amplification of DNA damage-inducible transcript 3 (DDIT3) is associated with myxoid liposarcoma-like morphology and homologous lipoblastic differentiation in dedifferentiated liposarcoma.
Dedifferentiated liposarcoma is defined as progression of atypical lipomatous tumor/well-differentiated liposarcoma to a higher grade usually non-lipogenic sarcoma, with amplification of 12q13-15. This region contains several genes involved in liposarcoma pathogenesis, including MDM2, CDK4, and DDIT...
| Publicado en: | Modern Pathology Vol. 32; no. 4; pp. 585 - 593 |
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| Autores principales: | , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Elsevier B.V.
Apr2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=135580570&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 135580570 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 08933952 UNB jtl: Modern Pathology issn: 08933952 maglogo: N pubinfo: dt: Apr2019 vid: 32 iid: 4 pid: 467 pub: Elsevier B.V. place: New York, New York artinfo: ui: 135580570 135580570 NLM30420727 135580570 10.1038/s41379-018-0171-y NLM30420727 135580570 ppf: 585 ppct: 8 formats: tig: atl: Amplification of DNA damage-inducible transcript 3 (DDIT3) is associated with myxoid liposarcoma-like morphology and homologous lipoblastic differentiation in dedifferentiated liposarcoma. aug: au: Mantilla, Jose G. Ricciotti, Robert W. Chen, Eleanor Y. Liu, Yajuan J. Hoch, Benjamin L. affil: Department of Pathology, University of Washington, Seattle, WA, USA sug: subj: Liposarcoma Pathology Liposarcoma Proteins Male Adult Aged Middle Age Liposarcoma, Myxoid Pathology Aged, 80 and Over Female Gene Amplification Human Adult: 19-44 years Aged: 65+ years Middle Aged: 45-64 years Aged, 80 & over Male Female ab: Dedifferentiated liposarcoma is defined as progression of atypical lipomatous tumor/well-differentiated liposarcoma to a higher grade usually non-lipogenic sarcoma, with amplification of 12q13-15. This region contains several genes involved in liposarcoma pathogenesis, including MDM2, CDK4, and DDIT3. While the former two are thought of as the main drivers in dedifferentiated liposarcoma, DDIT3 is typically rearranged in myxoid liposarcoma. Overexpression of DDIT3, along with MDM2 and CDK4, may contribute to the pathogenesis of dedifferentiated liposarcoma by interfering with adipocytic differentiation. Dedifferentiated liposarcoma with DDIT3 amplification has not been well characterized. In this study we evaluate the presence of DDIT3 amplification in 48 cases of dedifferentiated liposarcoma by cytogenomic microarray analysis and its correlation with demographic, clinical, and morphologic characteristics. Data from The Cancer Genome Atlas were also evaluated to determine a relationship between DDIT3 amplification and prognostic outcomes. Of the 48 cases, 16 (33%) had amplification of DDIT3; these patients were on average 11 years younger than patients without DDIT3 amplification (P < 0.05). Myxoid liposarcoma-like morphologic features were identified in 12/16 (75%) cases with DDIT3 amplification and in 7/32 (22%) cases without amplification (P < 0.05). Homologous lipoblastic differentiation was seen in 6/16 (38%) cases with DDIT3 amplification and 2/32 (6%) cases without it (P < 0.05). There was no significant correlation between DDIT3 amplification and tumor location, disease-specific or recurrence-free survival, and distant metastasis. DDIT3 amplification appears to interfere with the adipogenic molecular program and plays a role in inducing or maintaining a lipogenic phenotype in dedifferentiated liposarcoma. From a diagnostic standpoint, it is important to consider DDIT3-amplified dedifferentiated liposarcoma in the differential diagnosis of myxoid liposarcoma, particularly in small biopsies. Further studies evaluating the significance of DDIT3 amplification in the pathogenesis of dedifferentiated liposarcoma, as well as a potential predictor of tumor behavior in well-differentiated liposarcoma, are needed. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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