ABSTRACT Kinase inhibitors are accepted treatment for metastatic melanomas that harbor specifi c driver mutations in BRAF or KIT, but only 40% to 50% of cases are positive. To uncover other potential targetable mutations, we conducted whole-genome sequencing of a highly aggressive BRAF (V600) and KIT (W557, V559, L576, K642, and D816) wild-type melanoma. Surprisingly, we found a somatic BRAF L5...

The general responsiveness of human melanoma to immunotherapy has been well established, but active immunotherapy of melanoma has been hampered by insufficient information on the immunogenicity of melanoma-associated Ags in patients. In this study, we isolated a recombinant phage-Fab clone (A10-5) from a phage-Fab library derived from the B cells of a melanoma patient in remission after immunot...

High TIMP1 expression is associated with poor prognosis in melanoma, where it can bind to CD63 and β1 integrin, inducing PI3-kinase pathway and cell survival. Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), generated under phosphatidylinositol-3-kinase (PI3K) activation, enables the recruitment and activation of protein kinase B (PKB/AKT) and phosphoinositide-dependent kinase 1 (PDK1) at the...

Utilizing gene microarray profiling of melanoma samples, we have recently identified a novel gene overexpressed in both thick primary and metastatic melanomas. This gene, progestagen-associated endometrial protein (PAEP), has never before been implicated in the oncogenic processes of melanoma, with its true function in oncogenesis and tumour progression relatively unknown. Overexpression of the...

In 1889, the famous German Pathologist, Julius Cohnheim, postulated that the findings from tumor autopsy are explicable on natural principles. Within the next decade, members of the Johns Hopkins Hospital Medical Society with Dr. Flexner in the Chair dealt with a case that demonstrated the above dictum of Cohnheim. It is proposed here to appreciate historically what happened at the Meeting of F...

Melanoma is the most aggressive type of skin cancer, exhibiting extensive local invasion and early distant metastasis. Aberrant expression of ubiquitin-protein ligase E3C (UBE3C) plays a key role in tumor development and progression. In the present study, we analyzed UBE3C expression in samples of cancerous and normal skin tissue. Levels of UBE3C expression were much higher in primary and metas...

Molecular pathways regulating melanoma initiation and progression are potential targets of therapeutic development for this aggressive cancer. Identification and molecular analysis of these pathways in patients has been primarily restricted to targeted studies on individual proteins. Here, we report the most comprehensive analysis of formalin-fixed paraffin-embedded human melanoma tissues using...

Myeloid leukemia-1 (Mcl-1) is an anti-apoptotic protein implicated in tumor progression. Its expression was found to be elevated in many types of human cancers and is correlated with tumor progression. The expression of Mcl-1 in melanoma is not fully understood. We investigated the expression of Mcl-1 in normal nevi, dysplastic nevi, primary melanoma and melanoma metastases by tissue microarray...

Prediction of metastatic potential remains one of the main goals to be pursued in order to better assess the risk subgroups of patients with melanoma. Detection of occult melanoma cells in peripheral blood (circulating metastatic cells [CMC]) or in sentinel lymph nodes (sentinel node metastatic cells [SNMC]), could significantly contribute to better predict survival in melanoma patients. An ove...

Treatment of metastatic melanoma with inhibitors of the BRAF V600 oncogene in melanoma has been limited by the development of resistance. Combining the BRAF inhibitors with immunotherapy may prolong the response, but will acquisition of resistance to BRAF inhibitors also make melanoma cells resistant to immunotherapy?