Id family of helix-loop-helix proteins in cancer.

Over the past few decades, biologists have identified key molecular signatures associated with a wide range of human cancers. Recently, animal models have been particularly useful in establishing whether such signatures have functional relevance; the overexpression of pro-oncogenic or loss of anti-oncogenic factors have been evaluated for their effects on various tumour models. The aim of this review is to analyze the potential role of the inhibitor of DNA binding (Id) proteins in cancer and examine whether deregulated Id activity is tumorigenic and contributes to hallmarks of malignancy, such as loss of differentiation (anaplasia), unrestricted proliferation and neoangiogenesis.

Gangliogliomas: an intriguing tumor entity associated with focal epilepsies.

Gangliogliomas represent the most frequent tumor entity in young patients suffering from chronic focal epilepsies. In a series of 326 gangliogliomas collected from the University of Bonn Epilepsy Surgery Program and other departments of neuropathology in Germany, Austria, and Switzerland, epidemiological findings and histopathological hallmarks of gangliogliomas are systematically reviewed. The majority of these tumors occur within the temporal lobe and reveal a biphasic histological architecture characterized by a combination of dysplastic neurons and neoplastic glial cell elements. However, gangliogliomas exhibit a considerable variability in their histopathological appearance. Immunohistochemical studies are an important tool to discriminate these neoplasms from other tumor entities. Almost 80% of gangliogliomas reveal immunoreactivity for CD34, a stem cell epitope not expressed in normal brain. Immunohistochemical reactions for MAP2 or NeuN can be employed to characterize the dysplastic nature of neurons in those areas difficult to discriminate from pre-existing brain parenchyma. Less than 50% of the cases display binucleated neurons. With the frequent finding of "satellite" tumor clusters in adjacent brain regions, gangliogliomas are microscopically less circumscribed than previously assumed. The distinction from diffusely infiltrating gliomas is of considerable importance since tumor recurrence or malignant progression are rare events in gangliogliomas. Only little is known about the molecular pathogenesis of these glioneuronal tumors. Our findings support a dysontogenic origin from a glioneuronal precursor lesion with neoplastic, clonal proliferation of the glial cell population. Candidate genes appear to associate with neurodevelopmental signaling cascades rather than cell cycle control or DNA repair mechanisms. The reelin signaling and tuberin/insulin growth receptor pathways have recently been implicated in ganglioglioma development. Powerful new molecular genetic and biological tools can now be employed to unravel the pathogenesis of these intriguing lesions.