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Oncogenomic studies indicate that copy number variation (CNV) alters genes involved in tumor progression; however, identification of specific driver genes affected by CNV has been difficult, as these rearrangements are often contained in large chromosomal intervals among several bystander genes. Here, we addressed this problem and identified a CNV-targeted oncogene by performing comparative oncogenomics of human and zebrafish melanomas. We determined that the gene encoding growth differentiation factor 6 (GDF6), which is the ligand for the BMP family, is recurrently amplified and transcriptionally upregulated in melanoma. GDF6-induced BMP signaling maintained a trunk neural crest gene signature in melanomas. Additionally, GDF6 repressed the melanocyte differentiation gene MITF and the proapoptotic factor SOX9, thereby preventing differentiation, inhibiting cell death, and promoting tumor growth. GDF6 was specifically expressed in melanomas but not melanocytes. Moreover, GDF6 expression levels in melanomas were inversely correlated with patient survival. Our study has identified a fundamental role for GDF6 and BMP signaling in governing an embryonic cell gene signature to promote melanoma progression, thus providing potential opportunities for targeted therapy to treat GDF6-positive cancers.

Morphea, also known as localized scleroderma, is arare fibrosing disorder of the skin, the pathogenesisof which is incompletely understood. It is thought,however, to involve interplay of genetic dispositionand triggering environmental factors, such asinfections and autoimmunity. Pregnancy as a potentialtrigger has only been reported in four cases. Herein,we present a patient who developed morphea of thebreasts during pregnancy, which rapidly resolvedwith a normal delivery. Our patient was distinct fromsome of the reported patients because her conditionwas tightly correlated with her pregnancy, as judgingby rapid resolution after delivery. In addition, therewas no apparent infection, history of autoimmunity,or development of autoimmunity during or afterpregnancy. Although the pathogenesis of pregnancyassociatedmorphea is largely unknown, we exploredpotential mechanisms of this condition, which mayinvolve mechanical injury, “microchimerism,” andshifts in intrapartum hormones, such as TGF-β.

Lichen planus pigmentosus is a pigmentary disorder of unknown etiology, with diffuse hyperpigmentation of sun-exposed areas, more commonly seen in some ethnic and racial groups. We report an unusual case of lichen planus pigmentosus in a 40-year-old man with Fizpatrick type III skin that was present in a blaschkoid distribution on the trunk, a distribution that has been rarely reported. This unique presentation of lichen planus pigmentosus may contribute to better understanding of the etiology, as the blaschkoid distribution may reflect underlying cutaneous mosaicism that renders those cells more susceptible to an insult that results in lichen planus pigmentosus. This disorder should be considered in the differential diagnosis of macular hyperpigmentation, especially in those from more commonly affected ethnic and racial groups, even when the distribution is atypical and in the absence of history of sun exposure.

Toll-like receptors TLR7 and TLR9 are both implicated in the activation of autoreactive B cells and other cell types associated with systemic lupus erythematosus (SLE) pathogenesis. However, [Tlr9.sup.-/-] autoimmune-prone strains paradoxically develop more severe disease. We have now leveraged the negative regulatory role of TLR9 to develop an inducible rapid-onset murine model of systemic autoimmunity that depends on T cell detection of a membrane-bound OVA fusion protein expressed by MHC class [II.sup.+] cells, expression of TLR7, expression of the type I IFN receptor, and loss of expression of TLR9. These mice are distinguished by a high frequency of OVA-specific [Tbet.sup.+], [IFN-[gamma].sup.+], and FasL-expressing Th1 cells as well as autoantibody-producing B cells. Unexpectedly, contrary to what occurs in most models of SLE, they also developed skin lesions that are very similar to those of human cutaneous lupus erythematosus (CLE) as far as clinical appearance, histological changes, and gene expression. FasL was a key effector mechanism in the skin, as the transfer of FasL-deficient [DO11.sup.gld] T cells completely failed to elicit overt skin lesions. FasL was also upregulated in human CLE biopsies. Overall, our model provides a relevant system for exploring the pathophysiology of CLE as well as the negative regulatory role of TLR9., Introduction Cutaneous lupus erythematosus (CLE) refers to dermatologic features of systemic lupus erythematosus (SLE) that may or may not be associated with more systemic manifestations, such as arthritis, nephritis, or [...]

This article presents a case study of a 13-year-old girl with a polypoid papulonodule on her knee. The lesion had been gradually increasing in size and was surgically removed due to diagnostic uncertainty and the patient's request. The histopathology revealed a pleomorphic fibroma, a rare, benign cutaneous tumor. The article discusses the clinical features, histopathological characteristics, and treatment of pleomorphic fibroma, emphasizing the importance of surgical excision with clear margins. The authors also mention the potential association between pleomorphic fibroma and germline tumor protein 53 mutations. This case is unique as there have been no previous reports of pleomorphic fibroma in the pediatric population. [Extracted from the article]

Abstract Tumor necrosis factor alpha (TNF-[alpha]) inhibitors, such as infliximab, decrease the body's inflammatory response and thus the body's reaction to infection. Given the immune-mediated processes in psoriasis and psoriatic [...]