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Is CMV a target in pediatric glioblastoma? Expression of CMV proteins, pp65 and IE1-72 and CMV nucleic acids in a cohort of pediatric glioblastoma patients.

Publication ,  Journal Article
Wakefield, A; Pignata, A; Ghazi, A; Ashoori, A; Hegde, M; Landi, D; Gray, T; Scheurer, ME; Chintagumpala, M; Adesina, A; Gottschalk, S ...
Published in: J Neurooncol
November 2015

While the 5-year overall survival is better in pediatric than in adult patients diagnosed with glioblastoma (GBM), outcomes in children remain very poor. Understanding the mechanisms of tumorigenesis and tumor propagation can identify therapeutic targets to improve these outcomes. Human cytomegalovirus (CMV) proteins and nucleic acids are present in the majority of adult GBM. Indeed, CMV is emerging as a potential glioma-associated target for anti-CMV agents and cellular therapeutics. Furthermore, CMV appears to contribute to GBM's malignant phenotype, although its role in tumorigenesis is less certain. In this cohort of 25 serially diagnosed pediatric GBMs, the largest described cohort to date, we used immunohistochemical staining and in situ hybridization to show the presence of CMV antigens pp65 and IE1-72 as well as CMV nucleic acids, respectively. Our cohort indicated either CMV antigen pp65 or IE1-72 was present in approximately 67 % of pediatric GBM samples. The majority of samples stained positive for either CMV antigen showing a cytoplasmic pattern in 25-50 % of cells within the sample at a moderate intensity, while a few samples showed nuclear staining and higher grade/intensity. Of 16 samples where in situ hybridization was performed, 13 (81 %) showed specific staining using a CMV genome specific probe cocktail. ISH positive samples showed high concordance with being pp65 or IE1-72 positive. These findings, paired with the association of CMV expression with poor prognosis and overall survival, indicate the need to further investigate how these antigens are promoting tumor growth and preventing cell death. Also, the expression of these antigens in a majority of tumor tissues should be considered for immunotherapeutic targets in cases of pediatric GBM.

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Published In

J Neurooncol

DOI

EISSN

1573-7373

Publication Date

November 2015

Volume

125

Issue

2

Start / End Page

307 / 315

Location

United States

Related Subject Headings

  • Viral Matrix Proteins
  • Phosphoproteins
  • Oncology & Carcinogenesis
  • Male
  • Infant
  • Immediate-Early Proteins
  • Humans
  • Glioblastoma
  • Female
  • Cytomegalovirus
 

Citation

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Wakefield, A., Pignata, A., Ghazi, A., Ashoori, A., Hegde, M., Landi, D., … Ahmed, N. (2015). Is CMV a target in pediatric glioblastoma? Expression of CMV proteins, pp65 and IE1-72 and CMV nucleic acids in a cohort of pediatric glioblastoma patients. J Neurooncol, 125(2), 307–315. https://doi.org/10.1007/s11060-015-1905-z
Wakefield, Amanda, Antonella Pignata, Alexia Ghazi, Aidin Ashoori, Meenakshi Hegde, Daniel Landi, Tara Gray, et al. “Is CMV a target in pediatric glioblastoma? Expression of CMV proteins, pp65 and IE1-72 and CMV nucleic acids in a cohort of pediatric glioblastoma patients.J Neurooncol 125, no. 2 (November 2015): 307–15. https://doi.org/10.1007/s11060-015-1905-z.
Wakefield A, Pignata A, Ghazi A, Ashoori A, Hegde M, Landi D, et al. Is CMV a target in pediatric glioblastoma? Expression of CMV proteins, pp65 and IE1-72 and CMV nucleic acids in a cohort of pediatric glioblastoma patients. J Neurooncol. 2015 Nov;125(2):307–15.
Wakefield, Amanda, et al. “Is CMV a target in pediatric glioblastoma? Expression of CMV proteins, pp65 and IE1-72 and CMV nucleic acids in a cohort of pediatric glioblastoma patients.J Neurooncol, vol. 125, no. 2, Nov. 2015, pp. 307–15. Pubmed, doi:10.1007/s11060-015-1905-z.
Wakefield A, Pignata A, Ghazi A, Ashoori A, Hegde M, Landi D, Gray T, Scheurer ME, Chintagumpala M, Adesina A, Gottschalk S, Hicks J, Powell SZ, Ahmed N. Is CMV a target in pediatric glioblastoma? Expression of CMV proteins, pp65 and IE1-72 and CMV nucleic acids in a cohort of pediatric glioblastoma patients. J Neurooncol. 2015 Nov;125(2):307–315.
Journal cover image

Published In

J Neurooncol

DOI

EISSN

1573-7373

Publication Date

November 2015

Volume

125

Issue

2

Start / End Page

307 / 315

Location

United States

Related Subject Headings

  • Viral Matrix Proteins
  • Phosphoproteins
  • Oncology & Carcinogenesis
  • Male
  • Infant
  • Immediate-Early Proteins
  • Humans
  • Glioblastoma
  • Female
  • Cytomegalovirus