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The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans.

Carrasco, DR, Fenton, TR, Sukhdeo, K, Protopopova, M, Enos, M, You, MJ, Vizio, D Di, Nogueira, C, Stommel, J, Pinkus, GS, and others. (2006) The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans. Cancer Cell, 9 (5). pp. 379-390. ISSN 1535-6108. E-ISSN 1878-3686. (doi:10.1016/j.ccr.2006.03.028)

Abstract

Histiocytic sarcoma (HS) is a rare malignant proliferation of histiocytes of uncertain molecular pathogenesis. Here, genetic analysis of coincident loss of Pten and Ink4a/Arf tumor suppressors in the mouse revealed a neoplastic phenotype dominated by a premalignant expansion of biphenotypic myelolymphoid cells followed by the development of HS. Pten protein loss occurred only in the histiocytic portion of tumors, suggesting a stepwise genetic inactivation in the generation of HS. Similarly, human HS showed genetic or epigenetic inactivation of PTEN, p16(INK4A), and p14(ARF), supporting the relevance of this genetically engineered mouse model of HS. These genetic and translational observations establish a cooperative role of Pten and Ink4a/Arf in the development of HS and provide mechanistic insights into the pathogenesis of human HS.

Item Type: Article
DOI/Identification number: 10.1016/j.ccr.2006.03.028
Uncontrolled keywords: Animals, Cyclin-Dependent Kinase Inhibitor p16, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Histiocytic Disorders, Malignant, Homeostasis, Humans, Immunophenotyping, Lymphocytes, Methylation, Mice, Mutation, Myeloid Cells, PTEN Phosphohydrolase, Proto-Oncogene Proteins c-akt, Sarcoma, Tumor Suppressor Protein p14ARF
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Tim Fenton
Date Deposited: 23 May 2017 17:15 UTC
Last Modified: 29 May 2019 18:59 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/61524 (The current URI for this page, for reference purposes)
Fenton, TR: https://orcid.org/0000-0002-4737-8233
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