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Histone deacetylases expression in atypical teratoid rhabdoid tumors

Child's Nervous System volume 29, pages 5–9 (2013)Cite this article

Abstract

Purpose

Atypical teratoid rhabdoid tumors (ATRTs) are rare, highly malignant central nervous system tumors that occur during infancy and early childhood. Their poor outcome and resistance to conventional chemotherapies and radiotherapy, urges the development of new therapies. Recent studies have evaluated the effects of histone deacetylase inhibitors (HDACi) as a new potential treatment for ATRTs. However, most HDACi act unselectively against all, or at least several, histone deacetylase (HDAC) family members. We hypothesized that specific HDAC family members are deregulated in ATRT and therefore a more selective class of HDACi would be beneficial to patients with ATRT.

Methods

To test our hypothesis, we evaluated the expression level of different HDAC family members in ATRTs. Eight ATRTs were compared to six medulloblastoma samples in regards to the level of expression of the 18 HDAC family members as determined by microarray gene expression profiling.

Results

HDAC1 was the only member of the HDAC family to be significantly differentially expressed in ATRTs (FC = 4.728; p value = 0.00003).

Conclusions

A class of HDACi specifically targeting HDAC1 may allow for the desired therapeutic benefits with fewer side effects for children with ATRT.

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Fig. 1

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Acknowledgments

This project was supported by the Rally Foundation for Childhood Cancer Research in memory of Haley Trainer and Dr. Ralph & Marian C. Falk Medical Research Trust. We thank Chiang-Ching Huang PhD for statistical support and Veena Rajaram MD for histology review.

Ethical standards

This study has been approved by the Ann and Robert H. Lurie Children’s Hospital of Chicago Institutional Review Board (IRB#2009-13778) and had therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. All persons gave their informed consent prior to their inclusion in the study

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Affiliations

  1. Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children’s Hospital of Chicago, 225 E. Chicago Avenue, Box # 28, Chicago, IL, 60611, USA

    Simone Treiger Sredni & Tadanori Tomita

  2. Feinberg School of Medicine, Northwestern University, 420 East Superior Street, Chicago, IL, 60611, USA

    Simone Treiger Sredni, Maria de Fátima Bonaldo & Tadanori Tomita

  3. Cancer Biology and Epigenomics Program, Children’s Hospital of Chicago Research Center, 2430 North Halted Street, Chicago, IL, 60614, USA

    Simone Treiger Sredni, Abby L. Halpern, Christopher A. Hamm & Maria de Fátima Bonaldo

Authors
  1. Simone Treiger Sredni
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  2. Abby L. Halpern
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  3. Christopher A. Hamm
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  4. Maria de Fátima Bonaldo
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  5. Tadanori Tomita
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Correspondence to Simone Treiger Sredni.

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Sredni, S.T., Halpern, A.L., Hamm, C.A. et al. Histone deacetylases expression in atypical teratoid rhabdoid tumors. Childs Nerv Syst 29, 5–9 (2013). https://doi.org/10.1007/s00381-012-1965-8

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  • DOI: https://doi.org/10.1007/s00381-012-1965-8

Keywords

  • HDAC inhibitors
  • HDAC
  • ATRT
  • Rhabdoid tumor
  • Gene expression