Format

Send to

Choose Destination
Oncotarget. 2017 Jul 11;8(28):46065-46070. doi: 10.18632/oncotarget.17521.

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

Author information

1
Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX 77030, USA.
2
Department of Pediatrics, Division of Pediatric Hematology-Oncology, Baylor College of Medicine, Houston, TX 77030, USA.
3
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
4
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
5
Body and Nuclear Radiology Sections, Texas Children's Hospital, Houston, TX 77030, USA.
6
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
7
Center for Cell and Gene Therapy, Houston, TX 77030, USA.
8
Department of Oncological Sciences, Icahn School of Medicine, New York, NY 10029, USA.
9
Tisch Cancer Institute, Icahn School of Medicine, New York, NY 10029, USA.
10
Immunology Institute, Icahn School of Medicine, New York, NY 10029, USA.
11
Department of Dermatology, Icahn School of Medicine, New York, NY 10029, USA.

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.

KEYWORDS:

ERK activation; MAPK1; histiocytic disorder; juvenile xanthogranuloma; somatic mutation

PMID:
28512266
PMCID:
PMC5542249
DOI:
10.18632/oncotarget.17521
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center