Ligand-activated BMP signaling inhibits cell differentiation and death to promote melanoma.

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.

Pulp Obliteration in a Patient with Sclerodermatous Chronic Graft-versus-Host Disease.

Dental pulp calcification is a common finding associated with localized dental trauma, genetic disorders, and systemic inflammatory diseases. Chronic graft-versus-host disease (cGVHD) is a frequent complication after allogeneic hematopoietic cell transplantation (allo-HCT) characterized by immune-mediated injury to the skin, mouth, eyes, liver, and other tissues, resulting in significant disability and reduced quality of life. We report a patient with sclerodermatous cGVHD who presented with general pulp calcification in all teeth 5 years after allo-HCT. A review of full mouth dental radiographs obtained just before allo-HCT revealed normal-appearing pulp chambers. Based on prior reports of generalized pulp calcification associated with progressive systemic sclerosis, we hypothesized that the etiology was likely related to the presence of cGVHD with associated vascular and fibrotic tissue changes within the pulp vasculature. Clinicians should consider cGVHD in the differential diagnosis of generalized pulp calcification.

Reactive tonsillar enlargement showing strong 18F-FDG uptake during the follow-up of follicular lymphoma.

The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has become a standard procedure for the diagnosis, staging, and restaging in lymphoma patients. However, a relative high rate of false-positive results has been reported. We report a case of a 40-year-old man with a previous history of a nodal follicular lymphoma, stage IVA, treated with R-CHOP, which showed strong 18F-FDG uptake in the Waldeyer's tonsillar ring during his follow-up, being considered highly suspicious of relapsed lymphoma. A surgical removal of the palatine tonsils and adenoids was performed, which showed reactive follicular hyperplasia. Furthermore, bone marrow biopsy revealed absence of neoplasia. The patient is still in follow-up with no signs of recurrent lymphoma. This case illustrates that, despite the high sensitivity for the detection of recurrent lymphoma, 18F-FDG uptake should be interpreted with great caution and confirmatory studies should be performed before any therapy.