Etiology and Pathogenesis > Tumor Biology


Cancer Cell, Volume 9, Issue 6, 13 June 2006, Pages 473-484, Available online 12 June 2006; doi:10.1016/j.ccr.2006.04.021


Abstract

Oncogenic MITF dysregulation in clear cell sarcoma: Defining the MiT family of human cancers

Ian J. Davis1, 2, 4, Jessica J. Kim1, 2, Fatih Ozsolak1, 2, Hans R. Widlund1, 2, Orit Rozenblatt-Rosen3, Scott R. Granter5, Jinyan Du1, 2, Jonathan A. Fletcher2, 4, 5, Christopher T. Denny6, Stephen L. Lessnick7, W. Marston Linehan8, Andrew L. Kung2, 4 and David E. Fisher1, 2, 4,*

1Melanoma Program in Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115. 2Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115. 3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115. 4Division of Hematology/Oncology, Department of Medicine, Children's Hospital Boston, Boston, Massachusetts 02115. 5Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115. 6Department of Pediatrics, Division of Hematology/Oncology, Gwynne Hazen Cherry Memorial Labs, University of California, Los Angeles, Los Angeles, California 90095. 7Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, Utah 84112. 8Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892.
*Corresponding Author, Ph: 617 632 4916; Fax: 617 632 2085.
Received 11 January 2006;  revised 7 April 2006;  accepted 25 April 2006.  Published: June 12, 2006.


Clear cell sarcoma (CCS) harbors a pathognomonic chromosomal translocation fusing the Ewing's sarcoma gene (EWS) to the CREB family transcription factor ATF1 and exhibits melanocytic features. 
We show that EWS-ATF1 occupies the MITF promoter, mimicking melanocyte-stimulating hormone (MSH) signaling to induce expression of MITF, the melanocytic master transcription factor and an amplified oncogene in melanoma. 
Knockdown/rescue studies revealed that MITF mediates the requirement of EWS-ATF1 for CCS survival in vitro and in vivo as well as for melanocytic differentiation. 
Moreover, MITF and TFE3 reciprocally rescue one another in lines derived from CCS or pediatric renal carcinoma. 
Seemingly unrelated tumors thus employ distinct strategies to oncogenically dysregulate the MiT family, collectively broadening the definition of MiT-associated human cancers.

Author Keywords. DNA


Copyright © 2006 Elsevier B.V.
Abstract | News


 

HOME | Detection | Diagnosis | Epidemiology | Etiology & Pathogenesis | Integrative Medicine | Overall Mngt & Case Reports | Prevention | Prognosis | Psychosocial Aspects | Treatment 
About BrainLife
|
Children's Corner | E-mail Alerts | Journals | Newsletter | Patients & Caregivers | Search | Stem Cells | WHO Classification | SITEMAP