Trichoepithelioma : Molecular Pathogenesis
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Molecular Pathogenesis: Multiple familial trichoepitheliomas, Brooke-Spiegler syndrome and familial cylindromatosis all have mutations in the tumor suppressor gene CYLD on chromosome 16q12-q13. This suggests that the three conditions are probably related and represent a disease spectrum.
CYLD gene product is a deubiquitinating protein (i.e. it cleaves ubiquitin from its substrate) that interacts with TNF-alpha/NF-Kb pathway. It is involved in regulation of various important functions such as inflammation, cell survival, proliferation, and tumorigenesis. Loss of CYLD function leads to constitutive activation of NF-Kb pathway and decreased apoptosis leading to tumor formation.
Solitary Trichoepithelioma: The pathogenesis of solitary trichoepithelioma involves the sonic hedgehog signaling pathway. These tumors show somatic mutations and LOH of the patched (PTCH) gene and overexpression of GLI-1 protein (a zinc finger transcription factor that is the effector of hedgehog pathway).
CYLD gene product is a deubiquitinating protein (i.e. it cleaves ubiquitin from its substrate) that interacts with TNF-alpha/NF-Kb pathway. It is involved in regulation of various important functions such as inflammation, cell survival, proliferation, and tumorigenesis. Loss of CYLD function leads to constitutive activation of NF-Kb pathway and decreased apoptosis leading to tumor formation.
Solitary Trichoepithelioma: The pathogenesis of solitary trichoepithelioma involves the sonic hedgehog signaling pathway. These tumors show somatic mutations and LOH of the patched (PTCH) gene and overexpression of GLI-1 protein (a zinc finger transcription factor that is the effector of hedgehog pathway).