APC and CTNNB1 mutations are rare in sporadic ependymomas
ABSTRACT The ependymoma is the second most common malignant brain tumor of childhood; however, its molecular basis is poorly understood. The formation of multiple ependymomas has been reported as an occasional feature of Turcot syndrome type 2 (TS2), a familial cancer syndrome caused by inherited mutations of the APC tumor suppressor gene, and characterised by the concurrence of a primary CNS tumor (predominantly medulloblastoma) and multiple colorectal adenomas. APC is a critical component of the Wnt/Wingless signaling pathway, which is disrupted in sporadic cancers (e.g., colorectal adenomas, hepatocellular carcinomas, and medulloblastomas) by somatic mutations affecting multiple genes encoding alternative pathway components, including APC and CTNNB1 (encoding beta-catenin). To investigate any role for genetic disruption of the Wnt/Wingless pathway in sporadic ependymomas, we performed mutation analysis of APC and CTNNB1 in 77 primary tumors. Two synonymous APC polymorphisms (PRO1442PRO; THR1493THR) were identified, which were detected at equivalent rates in ependymomas and control nonneoplastic DNA samples (n =50); however, no further APC or CTNNB1 sequence variations were found. In summary, although inherited APC mutations may be associated with ependymoma development in certain TS2 cases, these data indicate that somatic mutations affecting APC and CTNNB1 do not play a major role in the pathogenesis of sporadic ependymomas.
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ABSTRACT: Turcot's syndrome is a rare clinical syndrome, characterized by the association between familial adenomatous polyposis (FAP) and a primary central nervous system tumour. Gardner's syndrome is characterized by the association between FAP and several tumour types such as multiple osteomas, fibromas, epidermoid cysts and desmoid tumours. We report here the case of a twenty-six year-old woman with a history of both Turcot's and Gardner syndromes. She had a family history of adenomatous polyposis with a mutation in the APC (Adenomatous Polyposis Coli) gene. At the age of 26, she presented a mucoepidermoid carcinoma of the right parotid gland in which the MECT1-MAML2 fusion was showed. We discuss the possible addition of this latter cancer type in the definition of Gardner's syndrome.Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 07/2013; DOI:10.1016/j.jcms.2013.05.012 · 1.25 Impact Factor
Chapter: Future Treatments of Ependymoma[Show abstract] [Hide abstract]
ABSTRACT: Although ependymoma is the third most common form of central nervous system (CNS) tumor, it is a poorly understood disease. The variable patterns of histology and clinical presentation, lack of consensus regarding appropriate means to stage and grade the disease, and the separation of pediatric and adult oncology services, have each hindered efforts to advance understanding of ependymoma biology and treatment. As a result, no new therapeutic approaches have been identified to treat ependymoma during the last 20 years and up to 40% of patients remain incurable (Brandes et al. 2005; Merchant and Fouladi 2005). The remarkable insensitivity of ependymoma to most nonsurgical conventional therapies has contributed further to this impasse in clinical management.12/2009: pages 291-304;
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ABSTRACT: Ependymomas are tumors that can present within either the intracranial or spinal regions. While 90% of all pediatric ependymomas are intracranial, spinal cord ependymomas are more commonly found in patients 20-40 years old. Treatment for spinal lesions has achieved local control rates up to 100% following gross total resection, while pediatric intracranial tumors have 40-60% mortality. Given the inability to effectively treat ependymomas with current standard practices, researchers have focused their efforts on evaluating chromosomal alterations, genetic expression profiles, epigenetic events, and molecular pathways. While these studies have provided critical insight into the potential mechanisms underlying ependymoma pathogenesis, understanding of the intricate interplay between the various pathways involved in tumor initiation, development, and progression will require deeper investigation. However, several potential prognostic markers and therapeutic targets have been identified, providing key areas of focus for future research. The utilization of unique genetic expression profiles based upon patient age, tumor location, tumor grade, and subtype has revealed a multitude of findings warranting further study. Inspection of various molecular pathways associated with ependymomas may establish the foundation for developing novel therapies capable of achieving significant clinical improvements with individualized regimens specifically designed for personalized treatment strategies.Clinical neurology and neurosurgery 01/2013; 115(4). DOI:10.1016/j.clineuro.2012.12.006 · 1.30 Impact Factor