Just Say No to ATOH: How HIC1 Methylation Might Predispose Medulloblastoma to Lineage Addiction
TLDR
Hypermethylated in cancer-1 (HIC1) is a tumor suppressor frequently targeted for promoter hypermethylation in medulloblastoma, an embryonal tumor of the cerebellum as discussed by the authors.Abstract:
Hypermethylated in cancer-1 (HIC1) is a tumor suppressor frequently targeted for promoter hypermethylation in medulloblastoma, an embryonal tumor of the cerebellum. Recently, we showed that HIC1 is a direct transcriptional repressor of ATOH1, a proneural transcription factor required for normal cerebellar development, as well as for medulloblastoma cell viability. Because demethylating agents can induce reexpression of silenced tumor suppressors, restoring HIC1 function may present an attractive therapeutic avenue in medulloblastoma by exploiting an apparent addiction to ATOH1. [Cancer Res 2008;68(21):8654–6]read more
Citations
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Book ChapterDOI
Cerebellum development and medulloblastoma.
TL;DR: This chapter will review the development of the cerebellar cortex, highlighting signaling pathways of potential relevance to tumorigenesis, and defining the extracellular cues and intracellular signaling pathways that control Cerebellar neurogenesis.
Journal ArticleDOI
Atoh1 inhibits neuronal differentiation and collaborates with Gli1 to generate medulloblastoma-initiating cells
TL;DR: By targeting multiple genes regulating the differentiation state of GNPs, Atoh1 collaborates with the pro-proliferative Gli1-dependent transcriptional program to influence medulloblastoma development.
Journal ArticleDOI
The Genetics of Hair Cell Development and Regeneration
TL;DR: The signals and molecular mechanisms that initiatehair cell development in vertebrates are described, with particular emphasis on the transcription factor Atoh1, which is both necessary and sufficient for hair cell development.
Journal ArticleDOI
Shh signaling protects Atoh1 from degradation mediated by the E3 ubiquitin ligase Huwe1 in neural precursors.
Antoine Forget,Laure Bihannic,Sara Maria Cigna,Coralie Lefevre,Marc Remke,Monia Barnat,Sophie Dodier,Hamasseh Shirvani,Audrey Mercier,Aurore Mensah,Mickael Garcia,Sandrine Humbert,Michael D. Taylor,Anna Lasorella,Olivier Ayrault +14 more
TL;DR: It is reported that SHH regulates Atoh1 stability by preventing its phosphodependent degradation by the E3 ubiquitin ligase Huwe1, and the crosstalk between SHH signaling and Atoh 1 during cerebellar development highlights a collaborative network that could be further targeted in medulloblastoma.
Journal ArticleDOI
Genome-wide high-resolution analysis of DNA copy number alterations in NF1-associated malignant peripheral nerve sheath tumors using 32K BAC array
Kiran Kumar Mantripragada,Teresita Díaz de Ståhl,Chris Patridge,Uwe Menzel,Robin Andersson,Nadia Chuzhanova,Lan Kluwe,Abhijit Guha,Victor F. Mautner,Jan P. Dumanski,Meena Upadhyaya +10 more
TL;DR: This is the first genome‐wide and high‐resolution analysis of DNA copy number alterations in MPNST using the 32K bacterial artificial chromosome microarray on a series of 24MPNSTs and three neurofibroma samples and found copy number gains were more frequent than deletions.
References
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TL;DR: The PATCHED (PTC) gene encodes a Sonic hedgehog (Shh) receptor and a tumor suppressor protein that is defective in basal cell nevus syndrome (BCNS).
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TL;DR: It is reported that mice lacking Math1 fail to form granule cells and are born with a cerebellum that is devoid of an external germinal layer, the first gene to be shown to be required in vivo for the genesis of granules cells, and hence the predominant neuronal population in the cerebellums.
Journal Article
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TL;DR: The fact that the samples from these two groups of patients were histologically indistinguishable, yet molecularly distinct, suggests that the occurrence of such hypermethylation may provide a clinical tool to identify patients with premalignant Barrett's who are at risk for further progression.