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 GNAQQ209L 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. GNAQQ209L 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‐creERT2, 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 GNAQQ209L. R26‐fs‐GNAQQ209L; Plp1‐creERT mice will be useful for defining biomarkers for potentially aggressive leptomeningeal melanocytomas and for developing new therapeutics for advanced disease.
Identifying genetic mosaicism is important in establishing a diagnosis, assessing recurrence risk, and providing accurate genetic counseling. Next-generation sequencing has allowed for the identification of mosaicism at levels below those detectable by conventional Sanger sequencing or chromosomal microarray analysis. The CAUSES Clinic was a pediatric translational trio-based genome-wide (exome or genome) sequencing study of 500 families (531 children) with suspected genetic disease at BC Children's and Women's Hospitals. Here we present 12 cases of apparent mosaicism identified in the CAUSES cohort: 9 cases of parental mosaicism for a disease-causing variant found in a child and 3 cases of mosaicism in the proband for a de novo variant. In 6 of these cases, there was no evidence of mosaicism on Sanger sequencing; the variant was not detected on Sanger sequencing in 3 cases, and it appeared to be heterozygous in 3 others. These cases are examples of 6 clinical manifestations of mosaicism: a proband with classical clinical features of mosaicism (e.g., segmental abnormalities of skin pigmentation or asymmetrical growth of bilateral body parts), a proband with unusually mild manifestations of a disease, a mosaic proband who is clinically indistinguishable from the constitutive phenotype, a mosaic parent with no clinical features of the disease, a mosaic parent with mild manifestations of the disease and a family in which both parents are unaffected and two siblings have the same disease-causing constitutional mutation. Our data demonstrates the importance of considering the possibility of mosaicism whenever exome or genome sequencing is performed and that its detection via genome-wide sequencing can permit more accurate genetic counseling.
This article attends to the possibilities that emerged from pedagogical invitation to the more-than-human in a qualitative inquiry course. We focus on the situated ethical and (micro)political grapplings that emerged from paying attention to the more-than-human alongside asymmetrical human and more-than-human lifeworlds. Our orientation toward the ethical and (micro)political is enacted through visual, poetic, and narrative storytelling that attempts to make visible what emerged for the students’ research and their becomings as qualitative inquirers in relation with course pedagogies. Our storytelling enacts a feminist practice that “stays with the trouble” stirred up by decentering the human while remaining accountable to enduring systemic, colonial, racialized, and gendered presences. While the particular lines of flight enacted by the pedagogical invitations in the course differed for each student, they come together in underlining the mattering of pedagogical and inquiry-based attunements toward the more-than-human within unequal worlds.
Anxieties associated with global conflict surround youth and ideological narratives mediating these conflicts can be seen in the popular media youth consume. This investigation uses contemporary cultural-theoretical conceptualizations of ideology to analyze several important popular screen-based cultural artifacts created for youth consumption to determine how young audiences are invited into the ideoscapes and discourses of global politics in the age of the “war on terror.” The analysis shows that these youth-oriented media artifacts script fundamental understandings of conflict and provide schema in which young viewers can orient themselves in relation to global Others, while also setting the matrix of intelligibility within which global politics itself becomes coherent. In addition, these popular cultural texts undertake an innovation of familiar Orientalisms, inviting young people to identify with an aggressive defense of the West and serving as an ideological support for the United States in the context of ongoing global conflicts.
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