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GNAQ Q209L expression initiated in multipotent neural crest cells drives aggressive melanoma of the central nervous system
Author(s) -
Urtatiz Oscar,
Cook Courtney,
Huang Jenny L.Y.,
Yeh Iwei,
Van Raamsdonk Catherine D.
Publication year - 2020
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12843
Subject(s) - neural crest , gnaq , melanocyte , biology , cancer research , melanoma , microbiology and biotechnology , microphthalmia associated transcription factor , central nervous system , pathology , neuroscience , medicine , genetics , transcription factor , mutation , embryo , gene
Primary leptomeningeal melanocytic neoplasms represent a spectrum of rare tumors originating from melanocytes of the leptomeninges, which are the inner two membranes that protect the central nervous system. Like other non‐epithelial melanocytic lesions, they bear frequent oncogenic mutations in the heterotrimeric G protein alpha subunits, GNAQ or GNA11 . In this study, we used Plp1‐creERT to force the expression of oncogenic GNAQ Q209L in the multipotent neural crest cells of the ventro‐medial developmental pathway, beginning prior to melanocyte cell differentiation. We found that this produces leptomeningeal melanocytic neoplasms, including cranial melanocytomas, spinal melanocytomas, and spinal melanomas, in addition to blue nevus‐like lesions in the dermis. GNAQ Q209L drove different phenotypes depending upon when during embryogenesis (E9.5, E10.5, or E11.5) it was induced by tamoxifen and which Cre driver ( Plp1‐creERT , Tyr‐creERT 2 , or Mitf‐cre ) was used. Given these differences, we propose that melanocytes go through temporary phases where they become sensitive to the oncogenic effects of GNAQ Q209L . R26 ‐ fs‐GNAQ Q209L ; Plp1‐creERT mice will be useful for defining biomarkers for potentially aggressive leptomeningeal melanocytomas and for developing new therapeutics for advanced disease.