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.

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.