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Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma.

Publication ,  Journal Article
Nakahara, Y; Northcott, PA; Li, M; Kongkham, PN; Smith, C; Yan, H; Croul, S; Ra, Y-S; Eberhart, C; Huang, A; Bigner, D; Grajkowska, W ...
Published in: Neoplasia
January 2010

Although medulloblastoma is the most common pediatric malignant brain tumor, its molecular underpinnings are largely unknown. We have identified rare, recurrent homozygous deletions of Kruppel-like Factor 4 (KLF4) in medulloblastoma using high-resolution single nucleotide polymorphism arrays, digital karyotyping, and genomic real-time polymerase chain reaction (PCR). Furthermore, we show that there is loss of physiological KLF4 expression in more than 40% of primary medulloblastomas both at the RNA and protein levels. Medulloblastoma cell lines drastically increase the expression of KLF4 in response to the demethylating agent 5-azacytidine and demonstrate dense methylation of the promoter CpG island by bisulfite sequencing. Methylation-specific PCR targeting the KLF4 promoter demonstrates CpG methylation in approximately 16% of primary medulloblastomas. Reexpression of KLF4 in the D283 medulloblastoma cell line results in significant growth suppression both in vitro and in vivo. We conclude that KLF4 is inactivated by either genetic or epigenetic mechanisms in a large subset of medulloblastomas and that it likely functions as a tumor suppressor gene in the pathogenesis of medulloblastoma.

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Published In

Neoplasia

DOI

EISSN

1476-5586

Publication Date

January 2010

Volume

12

Issue

1

Start / End Page

20 / 27

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Reverse Transcriptase Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Neoplasms, Experimental
  • Mice, Nude
  • Mice
  • Medulloblastoma
 

Citation

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Nakahara, Y., Northcott, P. A., Li, M., Kongkham, P. N., Smith, C., Yan, H., … Taylor, M. D. (2010). Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma. Neoplasia, 12(1), 20–27. https://doi.org/10.1593/neo.91122
Nakahara, Yukiko, Paul A. Northcott, Meihua Li, Paul N. Kongkham, Christian Smith, Hai Yan, Sidney Croul, et al. “Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma.Neoplasia 12, no. 1 (January 2010): 20–27. https://doi.org/10.1593/neo.91122.
Nakahara Y, Northcott PA, Li M, Kongkham PN, Smith C, Yan H, et al. Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma. Neoplasia. 2010 Jan;12(1):20–7.
Nakahara, Yukiko, et al. “Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma.Neoplasia, vol. 12, no. 1, Jan. 2010, pp. 20–27. Pubmed, doi:10.1593/neo.91122.
Nakahara Y, Northcott PA, Li M, Kongkham PN, Smith C, Yan H, Croul S, Ra Y-S, Eberhart C, Huang A, Bigner D, Grajkowska W, Van Meter T, Rutka JT, Taylor MD. Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma. Neoplasia. 2010 Jan;12(1):20–27.
Journal cover image

Published In

Neoplasia

DOI

EISSN

1476-5586

Publication Date

January 2010

Volume

12

Issue

1

Start / End Page

20 / 27

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Reverse Transcriptase Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Neoplasms, Experimental
  • Mice, Nude
  • Mice
  • Medulloblastoma