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

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• 作者：Daniel R. Carrasco ; Tim Fenton ; Kumar Sukhdeo ; Marina Protopopova ; Miriam Enos ; Mingjian J. You ; Dolores Divicio ; Cristina Nogueira ; Jayne Stommel ; Geraldine S. Pinkus ; Christopher Fletcher ; Jason L.
• 关键词：CELLCYCLE
• 刊名：Cancer Cell
• 出版年：2006
• 出版时间：May 2006
• 年：2006
• 卷：9
• 期：5
• 页码：379-390
• 全文大小：1278 K

文摘

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.