ABSTRACT
Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodeled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Altogether these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer.
Subject(s)
Enhancer Elements, Genetic/genetics , Histones/metabolism , Prostatic Neoplasms/genetics , Acetylation , Chromatin/genetics , Chromatin/metabolism , Disease-Free Survival , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Histones/genetics , Humans , Male , Nucleosomes/genetics , Nucleosomes/metabolism , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/mortality , Receptors, Androgen/genetics , Receptors, Androgen/metabolismABSTRACT
We report a case of a postmenopausal patient with hormone receptor-positive breast cancer who, while receiving tamoxifen, experienced relapse with isolated ovarian metastases 4.5 years after her primary treatment. After resection of her pelvic disease, she commenced anastrozole, and while receiving this, remained disease free for an additional 7.5 years before experiencing relapse again with isolated metastatic disease in an unusual location: intracardiac disease causing superior vena cava obstruction.
Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/secondary , Heart Neoplasms/secondary , Ovarian Neoplasms/secondary , Breast Neoplasms/therapy , Carcinoma, Ductal, Breast/therapy , Female , Heart Neoplasms/therapy , Humans , Middle Aged , Ovarian Neoplasms/therapy , Remission Induction , Treatment OutcomeABSTRACT
Ossifying fibromyxoid tumor is usually a benign tumor. However some of these tumors with histologic and clinical evidence of malignancy have also been reported and little information is available regarding surgery for metastatic ossifying fibromyxoid tumor. We present a case involving extensive excision of a huge metastatic ossifying fibromyxoid tumor occupying the upper mediastinum and upper half of the right hemithorax.
