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Identification of p18 INK4c as a tumor suppressor gene in glioblastoma multiforme.

Publication ,  Journal Article
Solomon, DA; Kim, J-S; Jenkins, S; Ressom, H; Huang, M; Coppa, N; Mabanta, L; Bigner, D; Yan, H; Jean, W; Waldman, T
Published in: Cancer Res
April 15, 2008

Genomic alterations leading to aberrant activation of cyclin/cyclin-dependent kinase (cdk) complexes drive the pathogenesis of many common human tumor types. In the case of glioblastoma multiforme (GBM), these alterations are most commonly due to homozygous deletion of p16(INK4a) and less commonly due to genomic amplifications of individual genes encoding cyclins or cdks. Here, we describe deletion of the p18(INK4c) cdk inhibitor as a novel genetic alteration driving the pathogenesis of GBM. Deletions of p18(INK4c) often occurred in tumors also harboring homozygous deletions of p16(INK4a). Expression of p18(INK4c) was completely absent in 43% of GBM primary tumors studied by immunohistochemistry. Lentiviral reconstitution of p18(INK4c) expression at physiologic levels in p18(INK4c)-deficient but not p18(INK4c)-proficient GBM cells led to senescence-like G(1) cell cycle arrest. These studies identify p18(INK4c) as a GBM tumor suppressor gene, revealing an additional mechanism leading to aberrant activation of cyclin/cdk complexes in this terrible malignancy.

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

April 15, 2008

Volume

68

Issue

8

Start / End Page

2564 / 2569

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Polymorphism, Single Nucleotide
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Mice, Transgenic
  • Mice
  • Glioblastoma
  • Genes, Tumor Suppressor
  • Flow Cytometry
  • Exons
 

Citation

APA
Chicago
ICMJE
MLA
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Solomon, D. A., Kim, J.-S., Jenkins, S., Ressom, H., Huang, M., Coppa, N., … Waldman, T. (2008). Identification of p18 INK4c as a tumor suppressor gene in glioblastoma multiforme. Cancer Res, 68(8), 2564–2569. https://doi.org/10.1158/0008-5472.CAN-07-6388
Solomon, David A., Jung-Sik Kim, Sultan Jenkins, Habtom Ressom, Michael Huang, Nicholas Coppa, Lauren Mabanta, et al. “Identification of p18 INK4c as a tumor suppressor gene in glioblastoma multiforme.Cancer Res 68, no. 8 (April 15, 2008): 2564–69. https://doi.org/10.1158/0008-5472.CAN-07-6388.
Solomon DA, Kim J-S, Jenkins S, Ressom H, Huang M, Coppa N, et al. Identification of p18 INK4c as a tumor suppressor gene in glioblastoma multiforme. Cancer Res. 2008 Apr 15;68(8):2564–9.
Solomon, David A., et al. “Identification of p18 INK4c as a tumor suppressor gene in glioblastoma multiforme.Cancer Res, vol. 68, no. 8, Apr. 2008, pp. 2564–69. Pubmed, doi:10.1158/0008-5472.CAN-07-6388.
Solomon DA, Kim J-S, Jenkins S, Ressom H, Huang M, Coppa N, Mabanta L, Bigner D, Yan H, Jean W, Waldman T. Identification of p18 INK4c as a tumor suppressor gene in glioblastoma multiforme. Cancer Res. 2008 Apr 15;68(8):2564–2569.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

April 15, 2008

Volume

68

Issue

8

Start / End Page

2564 / 2569

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Polymorphism, Single Nucleotide
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Mice, Transgenic
  • Mice
  • Glioblastoma
  • Genes, Tumor Suppressor
  • Flow Cytometry
  • Exons