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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Aged, 80 and over, Apoptosis, Carcinoma, Merkel Cell, Carcinoma, Neuroendocrine, Case-Control Studies, DNA Repair, Epigenesis, Genetic, European Continental Ancestry Group, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Mutation, Retrospective Studies, Skin Neoplasms.
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Is neuroendocrine Merkel cell carcinoma associated with mutations in key DNA repair , epigenetic and apoptosis pathways : a case-based study using targeted massively parallel sequencing? Context: Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma with a poorly understood molecular etiology. We implemented a comprehensive deep sequencing approach to identify mutations in the tumor DNA from a cohort of patients treated at our institution over the past 15 years. Our results indicate mutations that may constitute therapeutic targets in MCC. Five patients were treated for MCC within the study interval. Patients with adequate tissue (n = 4), positive neuroendocrine differentiation (chromogranin, synaptophysin, and cytokeratin 20), and histopathological confirmation of MCC were included in the study. DNA was extracted from archival tumor tissue samples and analyzed by massively parallel sequencing using a targeted, multiplex PCR approach followed by semiconductor sequencing. We demonstrate high-penetrance nonsense mutations in PDE4DIP (n = 4) as well as various missense mutations in the DNA damage response (PRKDC, AURKB, ERCC5, ATR, and ATRX) and epigenetic modulating enzymes (MLL3).
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We describe several mutations in potential disease-relevant genes and pathways. These targets should be evaluated in a larger cohort to determine their role in the molecular pathogenesis of MCC. Final Decision: yes