The histone variant macroH2A suppresses melanoma progression through regulation of CDK8.

Cancer is a disease consisting of both genetic and epigenetic changes. Although increasing evidence demonstrates that tumour progression entails chromatin-mediated changes such as DNA methylation, the role of histone variants in cancer initiation and progression currently remains unclear. Histone variants replace conventional histones within the nucleosome and confer unique biological functions to chromatin. Here we report that the histone variant macroH2A (mH2A) suppresses tumour progression of malignant melanoma. Loss of mH2A isoforms, histone variants generally associated with condensed chromatin and fine-tuning of developmental gene expression programs, is positively correlated with increasing malignant phenotype of melanoma cells in culture and human tissue samples. Knockdown of mH2A isoforms in melanoma cells of low malignancy results in significantly increased proliferation and migration in vitro and growth and metastasis in vivo. Restored expression of mH2A isoforms rescues these malignant phenotypes in vitro and in vivo. We demonstrate that the tumour-promoting function of mH2A loss is mediated, at least in part, through direct transcriptional upregulation of CDK8. Suppression of CDK8, a colorectal cancer oncogene, inhibits proliferation of melanoma cells, and knockdown of CDK8 in cells depleted of mH2A suppresses the proliferative advantage induced by mH2A loss. Moreover, a significant inverse correlation between mH2A and CDK8 expression levels exists in melanoma patient samples. Taken together, our results demonstrate that mH2A is a critical component of chromatin that suppresses the development of malignant melanoma, a highly intractable cutaneous neoplasm.

Verruciform xanthoma in the setting of cutaneous trauma and chronic inflammation: report of a patient and a brief review of the literature.

We report a rare case of multiple, co-exisitng verruciform xanthomas (VXs) of the anogenital region in the setting of cutaneous trauma. VX is a rare benign mucocutaneous neoplasm that typically presents as a solitary lesion with a predilection for the oral cavity, although extra-oral lesions have been reported involving the vulva, scrotum, penis, anal region and extremities. The etiology and pathogenesis of VX have yet to be determined; however, recent literature has reported that multifocal cutaneous VX are frequently associated with pre-existing inflammatory processes. A significant number of VXs of the skin have been found to co-exist with cutaneous disorders including graft vs. host disease, discoid lupus erythematosus, pemphigus vulgaris, and recessive dystrophic epidermolysis bullosa. Therefore, we speculate severe cutaneous trauma and chronic inflammation may induce epithelial keratinocytes to respond aberrantly leading to epidermal hyperplasia and foamy cell formation characterizing the VX lesion.

Mohs micrographic surgery for the management of nonmelanoma skin cancers.

Many treatment modalities have been described to address the growing epidemic of nonmelanoma skin cancer (NMSC). Mohs micrographic surgery (MMS) is a surgical technique that allows complete and precise microscopic margin analysis by using horizontal frozen sections. The purpose of MMS is twofold: to ensure definitive excision and to minimize loss of normal surrounding tissue. MMS offers the advantages of superior cure rates and, because tissue removal is minimized, excellent cosmetic outcomes. Therefore, MMS has become the treatment of choice for many high-risk tumors. Because this technique is labor intensive, MMS is not indicated in certain situations. Understanding the indications, advantages, and disadvantages of MMS remains paramount for facial plastic surgeons managing NMSC.