NUT midline carcinoma (NMC) is an aggressive type of squamous cell carcinoma that is defined by the presence of BRD-NUT fusion oncogenes, which encode chimeric proteins that block differentiation and ...maintain tumor growth. BRD-NUT oncoproteins contain two bromodomains whose binding to acetylated histones is required for the blockade of differentiation in NMC, but the mechanisms by which BRD-NUT act remain uncertain. Here, we provide evidence that MYC is a key downstream target of BRD4-NUT. Expression profiling of NMCs shows that the set of genes whose expression is maintained by BRD4-NUT is highly enriched for MYC upregulated genes, and MYC and BRD4-NUT protein expression is strongly correlated in primary NMCs. More directly, we find that BRD4-NUT associates with the MYC promoter and is required to maintain MYC expression in NMC cell lines. Moreover, both siRNA knockdown of MYC and a dominant-negative form of MYC, omomyc, induce differentiation of NMC cells. Conversely, differentiation of NMC cells induced by knockdown of BRD4-NUT is abrogated by enforced expression of MYC. Together, these findings suggest that MYC is a downstream target of BRD4-NUT that is required for maintenance of NMC cells in an undifferentiated, proliferative state. Our findings support a model in which dysregulation of MYC by BRD-NUT fusion proteins has a central role in the pathogenesis of NMC.
This case raises awareness of the diagnosis of sternal fracture during labor and obviates the need for lengthy, expense-consuming workup. This report identifies a subset of women who may be at higher ...risk for this pathology.
Upon diagnosing and treating a patient who spontaneously fractured her sternum during labor, we reviewed previously reported cases and highlight key points of this entity.
We report the third case of sternal fracture during labor in a healthy primigravida with female athlete triad. After 12 h of labor, the woman underwent epidural placement. By 16 h, the cervix was fully dilated. During the second push in the chin-to-chest position, a healthy baby was delivered, but the mother experienced acute anterior chest pain. Tenderness persisted for three weeks. Plain radiographs confirmed the presence of the fracture, which healed spontaneously.
While chest pain during labor often results from serious causes including pulmonary embolism, myocardial infarction, and spontaneous pneumothorax, hyperflexion sternal fracture can occur, particularly in a woman with female athlete triad.
•Spontaneous sternal fracture is a rare cause of acute chest pain during labor.•Women with the female athlete triad may be prone to sternal fracture during labor.•Early diagnosis and conservative care are key in labor-induced sternal fractures.
INTRODUCTIONThis case raises awareness of the diagnosis of sternal fracture during labor and obviates the need for lengthy, expense-consuming workup. This report identifies a subset of women who may ...be at higher risk for this pathology. METHODSUpon diagnosing and treating a patient who spontaneously fractured her sternum during labor, we reviewed previously reported cases and highlight key points of this entity. RESULTSWe report the third case of sternal fracture during labor in a healthy primigravida with female athlete triad. After 12 h of labor, the woman underwent epidural placement. By 16 h, the cervix was fully dilated. During the second push in the chin-to-chest position, a healthy baby was delivered, but the mother experienced acute anterior chest pain. Tenderness persisted for three weeks. Plain radiographs confirmed the presence of the fracture, which healed spontaneously. CONCLUSIONWhile chest pain during labor often results from serious causes including pulmonary embolism, myocardial infarction, and spontaneous pneumothorax, hyperflexion sternal fracture can occur, particularly in a woman with female athlete triad.
PDF
