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

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. Hornick; Webster K. Cavenee; Frank B. Furnari; Ronald A. DePinho

doi:10.1016/j.ccr.2006.03.028

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

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. Hornick, Webster K. Cavenee, Frank B. Furnari, Ronald A. DePinho

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

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.

Original language	English (US)
Pages (from-to)	379-390
Number of pages	12
Journal	Cancer cell
Volume	9
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2006.03.028
State	Published - May 2006
Externally published	Yes

Keywords

CELLCYCLE

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2006.03.028

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Carrasco, D. R., Fenton, T., Sukhdeo, K., Protopopova, M., Enos, M., You, M. J., Divicio, D., Nogueira, C., Stommel, J., Pinkus, G. S., Fletcher, C., Hornick, J. L., Cavenee, W. K., Furnari, F. B., & DePinho, R. A. (2006). The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans. Cancer cell, 9(5), 379-390. https://doi.org/10.1016/j.ccr.2006.03.028

Carrasco, DR, Fenton, T, Sukhdeo, K, Protopopova, M, Enos, M, You, MJ, Divicio, D, Nogueira, C, Stommel, J, Pinkus, GS, Fletcher, C, Hornick, JL, Cavenee, WK, Furnari, FB & DePinho, RA 2006, 'The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans', Cancer cell, vol. 9, no. 5, pp. 379-390. https://doi.org/10.1016/j.ccr.2006.03.028

@article{b3172280466345fea30b14a50912c632,

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

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, p16INK4A, and p14ARF, 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.",

keywords = "CELLCYCLE",

author = "Carrasco, {Daniel R.} and Tim Fenton and Kumar Sukhdeo and Marina Protopopova and Miriam Enos and You, {Mingjian J.} and Dolores Divicio and Cristina Nogueira and Jayne Stommel and Pinkus, {Geraldine S.} and Christopher Fletcher and Hornick, {Jason L.} and Cavenee, {Webster K.} and Furnari, {Frank B.} and DePinho, {Ronald A.}",

note = "Funding Information: We wish to thank N. Bardeesy, G. Tonon, R.A. Aguirre, R. Kollipara, and E. Farazi for valuable comments on the manuscript; Robert Bachoo for providing Pten −/− cells; and Ilana Perna for technical assistance. R.A.D. is an American Cancer Society Research Professor and an Ellison Medical Foundation Senior Scholar. This work was supported by the Bennett LeBow Fund to Cure Myeloma (R.A.D.), NIH grants P01 CA95616 (R.A.D., F.B.F., and W.K.C.), and U01 CA84313 (R.A.D.). W.K.C. is a Fellow of the National Foundation for Cancer Research, and F.B.F. is partially supported by the Goldhirsh Foundation. D.R.C. is supported by a Mentored Clinician Scientist Award (K08AG0103) and is a Sidney Kimmel Foundation Scholar. ",

year = "2006",

month = may,

doi = "10.1016/j.ccr.2006.03.028",

language = "English (US)",

volume = "9",

pages = "379--390",

journal = "Cancer cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans

AU - Carrasco, Daniel R.

AU - Fenton, Tim

AU - Sukhdeo, Kumar

AU - Protopopova, Marina

AU - Enos, Miriam

AU - You, Mingjian J.

AU - Divicio, Dolores

AU - Nogueira, Cristina

AU - Stommel, Jayne

AU - Pinkus, Geraldine S.

AU - Fletcher, Christopher

AU - Hornick, Jason L.

AU - Cavenee, Webster K.

AU - Furnari, Frank B.

AU - DePinho, Ronald A.

N1 - Funding Information: We wish to thank N. Bardeesy, G. Tonon, R.A. Aguirre, R. Kollipara, and E. Farazi for valuable comments on the manuscript; Robert Bachoo for providing Pten −/− cells; and Ilana Perna for technical assistance. R.A.D. is an American Cancer Society Research Professor and an Ellison Medical Foundation Senior Scholar. This work was supported by the Bennett LeBow Fund to Cure Myeloma (R.A.D.), NIH grants P01 CA95616 (R.A.D., F.B.F., and W.K.C.), and U01 CA84313 (R.A.D.). W.K.C. is a Fellow of the National Foundation for Cancer Research, and F.B.F. is partially supported by the Goldhirsh Foundation. D.R.C. is supported by a Mentored Clinician Scientist Award (K08AG0103) and is a Sidney Kimmel Foundation Scholar.

PY - 2006/5

Y1 - 2006/5

N2 - 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, p16INK4A, and p14ARF, 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.

AB - 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, p16INK4A, and p14ARF, 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.

KW - CELLCYCLE

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U2 - 10.1016/j.ccr.2006.03.028

DO - 10.1016/j.ccr.2006.03.028

M3 - Article

C2 - 16697958

AN - SCOPUS:33646358695

SN - 1535-6108

VL - 9

SP - 379

EP - 390

JO - Cancer cell

JF - Cancer cell

IS - 5

ER -

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

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