Oncotarget

Research Papers:

Activating MAPK1 (ERK2) mutation in an aggressive case of disseminated juvenile xanthogranuloma

Rikhia Chakraborty, Oliver A. Hampton, Harshal Abhyankar, Daniel J. Zinn, Amanda Grimes, Brooks Skull, Olive Eckstein, Nadia Mahmood, David A. Wheeler, Dolores Lopez-Terrada, Tricia L. Peters, John M. Hicks, Tarek Elghetany, Robert Krance, Poulikos I. Poulikakos, Miriam Merad, Kenneth L. McClain, Carl E. Allen and Williams D. Parsons _

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Oncotarget. 2017; 8:46065-46070. https://doi.org/10.18632/oncotarget.17521

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Abstract

Rikhia Chakraborty1,2, Oliver A. Hampton3,5, Harshal Abhyankar1,2, Daniel J. Zinn1,2, Amanda Grimes1,2, Brooks Skull1,2, Olive Eckstein1,2, Nadia Mahmood6, David A. Wheeler3,5, Dolores Lopez-Terrada1,4, Tricia L. Peters4, John M. Hicks4, Tarek Elghetany4, Robert Krance1,2,7, Poulikos I. Poulikakos8,9,10, Miriam Merad8,9,11, Kenneth L. McClain1,2, Carl E. Allen1,2 and Donald W. Parsons1,2,3,4,5

1Texas Children’s Cancer Center, Texas Children’s Hospital, Houston, TX 77030, USA

2Department of Pediatrics, Division of Pediatric Hematology-Oncology, Baylor College of Medicine, Houston, TX 77030, USA

3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA

4Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA

5Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA

6Body and Nuclear Radiology Sections, Texas Children’s Hospital, Houston, TX 77030, USA

7Center for Cell and Gene Therapy, Houston, TX 77030, USA

8Department of Oncological Sciences, Icahn School of Medicine, New York, NY 10029, USA

9Tisch Cancer Institute, Icahn School of Medicine, New York, NY 10029, USA

10Immunology Institute, Icahn School of Medicine, New York, NY 10029, USA

11Department of Dermatology, Icahn School of Medicine, New York, NY 10029, USA

Correspondence to:

Donald W. Parsons, email: [email protected]

Carl E. Allen, email: [email protected]

Keywords: juvenile xanthogranuloma, MAPK1, ERK activation, histiocytic disorder, somatic mutation

Received: October 13, 2016     Accepted: March 13, 2017     Published: April 29, 2017

ABSTRACT

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder that is usually benign and self-limiting. We present a case of atypical, aggressive JXG harboring a novel mitogen-activated protein kinase (MAPK) pathway mutation in the MAPK1 gene, which encodes mitogen-activated protein kinase 1 or extracellular signal-regulated 2 (ERK2). Our analysis revealed that the mutation results in constitutive ERK activation that is resistant to BRAF or MEK inhibitors but susceptible to an ERK inhibitor. These data highlight the importance of identifying specific MAPK pathway alterations as part of the diagnostic workup for patients with histiocytic disorders rather than initiating empiric treatment with MEK inhibitors.


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