Lineage of origin in rhabdomyosarcoma informs pharmacological response

被引：87

作者：

Abraham, Jinu ^{[1
]}

Nunez-Alvarez, Yaiza ^{[2
]}

Hettmer, Simone ^{[3
,4
]}

Carrio, Elvira ^{[2
]}

Chen, Hung-I Harry ^{[5
]}

Nishijo, Koichi ^{[5
]}

Huang, Elaine T. ^{[1
]}

Prajapati, Suresh I. ^{[5
]}

Walker, Robert L. ^{[6
]}

Davis, Sean ^{[6
]}

Rebeles, Jennifer ^{[5
]}

Wiebush, Hunter ^{[5
]}

McCleish, Amanda T. ^{[5
]}

Hampton, Sheila T. ^{[5
]}

Bjornson, Christopher R. R. ^{[7
]}

Brack, Andrew S. ^{[7
]}

Wagers, Amy J. ^{[3
]}

Rando, Thomas A.

Capecchi, Mario R. ^{[8
]}

Marini, Frank C. ^{[9
]}

Ehler, Benjamin R. ^{[10
]}

Zarzabal, Lee Ann ^{[10
]}

Goros, Martin W. ^{[10
]}

Michalek, Joel E. ^{[10
]}

Meltzer, Paul S. ^{[6
]}

Langenau, David M. ^{[11
]}

LeGallo, Robin D. ^{[12
]}

Mansoor, Atiya ^{[13
]}

Chen, Yidong ^{[5
,10
]}

Suelves, Monica ^{[2
]}

Rubin, Brian P. ^{[14
]}

Keller, Charles ^{[1
]}

机构：

[1] Oregon Hlth & Sci Univ, Pape Family Pediat Res Inst, Pediat Canc Biol Program, Dept Pediat, Portland, OR 97239 USA

[2] Germans I Trias Pujol Hlth Sci Res Inst IGTP, IMPPC, Badalona 08916, Spain

[3] Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Joslin Diabet Ctr,Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[4] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Div Pediat Hematol Oncol, Boston, MA 02115 USA

[5] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA

[6] Natl Canc Inst, Oncogen Sect, Pediat Oncol Branch, Adv Technol Ctr, Gaithersburg, MD 20877 USA

[7] Stanford Univ, Dept Neurol, Dept Neurol Sci, Glenn Labs Biol Aging, Palo Alto, CA 94304 USA

[8] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA

[9] Wake Forest Univ, Bowman Gray Sch Med, Inst Regenerat Med, Winston Salem, NC 27157 USA

[10] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA

[11] Massachusetts Gen Hosp, Ctr Canc Res, Dept Pathol, Charlestown, MA 02129 USA

[12] Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA

[13] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA

[14] Cleveland Clin Fdn, Lerner Res Inst, Taussig Canc Ctr, Dept Anat Pathol,Dept Mol Genet, Cleveland, OH 44195 USA

来源：

GENES & DEVELOPMENT | 2014年 / 28卷 / 14期

关键词：

alveolar rhabdomyosarcoma; Pax3:Foxo1; sarcoma; satellite cell; myoblast; histone; CHILDRENS ONCOLOGY GROUP; ALVEOLAR RHABDOMYOSARCOMA; EMBRYONAL RHABDOMYOSARCOMA; SATELLITE CELLS; MOUSE MODEL; STEM-CELLS; MUSCLE DIFFERENTIATION; EXPRESSION SIGNATURE; PAX7; EXPRESSION; BREAST-CANCER;

D O I：

10.1101/gad.238733.114

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Lineage or cell of origin of cancers is often unknown and thus is not a consideration in therapeutic approaches. Alveolar rhabdomyosarcoma (aRMS) is an aggressive childhood cancer for which the cell of origin remains debated. We used conditional genetic mouse models of aRMS to activate the pathognomonic Pax3:Foxo1 fusion oncogene and inactivate p53 in several stages of prenatal and postnatal muscle development. We reveal that lineage of origin significantly influences tumor histomorphology and sensitivity to targeted therapeutics. Furthermore, we uncovered differential transcriptional regulation of the Pax3:Foxo1 locus by tumor lineage of origin, which led us to identify the histone deacetylase inhibitor entinostat as a pharmacological agent for the potential conversion of Pax3:Foxo1-positive aRMS to a state akin to fusion-negative RMS through direct transcriptional suppression of Pax3:Foxo1.

引用

页码：1578 / 1591

页数：14

共 62 条

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Evasion Mechanisms to Igf1r Inhibition in Rhabdomyosarcoma [J].