The Drosophila EGF receptor (DER) is activated by secreted Spitz to induce different cell fates in the ventral ectoderm. Processing of the precursor transmembrane Spitz to generate the secreted form was shown to be the limiting event, but the cells in which processing takes place and the mechanism that may generate a gradient of secreted Spitz in the ectoderm were not known. The ectodermal defe...

BACKGROUND The relationships between so-called spitzoid tumours have proven difficult to understand. OBJECTIVES To address three questions: does spitzoid tumour morphological similarity reflect molecular similarity? Does Spitz naevus progress into spitzoid melanoma? Are ambiguous spitzoid tumours genuine entities? METHODS BRAF, NRAS and HRAS mutations were analysed using single-strand confo...

BACKGROUND Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3 ), a member of the insulin-like growth factor mRNA-binding protein family, is expressed in several human malignancies, including melanomas. However, the expression of IMP-3 has not been explored in melanoma in situ, various histologic subtypes of invasive melanomas and atypical Spitz tumors. METHODS IMP-3 immunostain was p...

© 2012 The Authors. doi: 10.2340/00015555-1264 Journal Compilation © 2012 Acta Dermato-Venereologica. ISSN 0001-5555 Spitz nevus (SN) was first described in 1948, and was referred to as melanoma of childhood (1). Although SNs are benign melanocytic neoplasms, these lesions share many histopathological findings with malignant melanomas (MMs) (2). Despite the diagnostic criteria, the similarities...

Recent studies have clarified how the active form of the Drosophila EGF receptor ligand Spitz is produced: Star chaperones Spitz in the ER and mediates its transport to the Golgi, where the intramembrane serine protease Rhomboid cleaves the Spitz proprotein to initiate secretion.

Argos, a secreted inhibitor of the Drosophila epidermal growth factor receptor, and the only known secreted receptor tyrosine kinase inhibitor, acts by sequestering the EGFR ligand Spitz. We use computational modeling to show that this biochemically-determined mechanism of Argos action can explain available genetic data for EGFR/Spitz/Argos interactions in vivo. We find that efficient Spitz seq...

BACKGROUND Spindle and/or epithelioid melanocytic proliferations that display overlapping histopathologic features of Spitz nevus and Spitz-like melanoma are diagnostically difficult and controversial melanocytic tumors. There are reports of such lesions metastasizing to regional lymph nodes, with a few widely disseminating, resulting in death. METHODS The authors reviewed clinical and histop...

Lipid modifications such as palmitoylation or myristoylation target intracellular proteins to cell membranes. Secreted ligands of the Hedgehog and Wnt families are also palmitoylated; this modification, which requires the related transmembrane acyltransferases Rasp and Porcupine, can enhance their secretion, transport, or activity. We show here that rasp is also essential for the developmental ...

In 1989 Clark et al, 1 in a landmark article, used multivari-ate analysis and logistic regression to generate a model predicting survival in stage I primary malignant melanoma. They examined 23 attributes and found that, in addition to tumor thickness, 5, including mitotic rate, presence of tumor-infiltrating lymphocytes, anatomic site of the lesion, sex of the patient, and histologic evidence ...