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

TitleActivating MAPK1 (ERK2) mutation in an aggressive case of disseminated juvenile xanthogranuloma.
Publication TypeJournal Article
Year of Publication2017
AuthorsChakraborty, R, Hampton, OA, Abhyankar, H, Zinn, DJ, Grimes, A, Skull, B, Eckstein, O, Mahmood, N, Wheeler, DA, López-Terrada, D, Peters, TL, Hicks, JM, Elghetany, T, Krance, R, Poulikakos, PI, Merad, M, McClain, KL, Allen, CE, Parsons, DW
JournalOncotarget
Volume8
Issue28
Pagination46065-46070
Date Published2017 Jul 11
ISSN1949-2553
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.

DOI10.18632/oncotarget.17521
Alternate JournalOncotarget
PubMed ID28512266
PubMed Central IDPMC5542249
Grant ListR01 CA154489 / CA / NCI NIH HHS / United States
R01 CA154947 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
P50 CA126752 / CA / NCI NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States