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.
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.
Texas Children's Hospital, Houston Methodist Hospital, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Street MC 3-3320, Houston, TX, 77030, USA.|Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
Amanda
A
Wakefield
Texas Children's Hospital, Houston Methodist Hospital, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Street MC 3-3320, Houston, TX, 77030, USA.|Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
Antonella
A
Pignata
Texas Children's Hospital, Houston Methodist Hospital, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Street MC 3-3320, Houston, TX, 77030, USA.|Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
Alexia
A
Ghazi
Texas Children's Hospital, Houston Methodist Hospital, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Street MC 3-3320, Houston, TX, 77030, USA.|Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
Aidin
A
Ashoori
Texas Children's Hospital, Houston Methodist Hospital, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Street MC 3-3320, Houston, TX, 77030, USA.|Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
Meenakshi
M
Hegde
Texas Children's Hospital, Houston Methodist Hospital, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Street MC 3-3320, Houston, TX, 77030, USA.|Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
Daniel
D
Landi
Texas Children's Hospital, Houston Methodist Hospital, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Street MC 3-3320, Houston, TX, 77030, USA.|Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
Tara
T
Gray
Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
Michael E
ME
Scheurer
Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
Murali
M
Chintagumpala
Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pathology and Immunology, Baylor College of Medicine, Houston, TX, 77030, USA.
Adekunle
A
Adesina
Texas Children's Hospital, Houston Methodist Hospital, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Street MC 3-3320, Houston, TX, 77030, USA.|Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pathology and Immunology, Baylor College of Medicine, Houston, TX, 77030, USA.
Stephen
S
Gottschalk
Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.|Departments of Pathology and Immunology, Baylor College of Medicine, Houston, TX, 77030, USA.
John
J
Hicks
Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, 77030, USA.
Suzanne Z
SZ
Powell
Texas Children's Hospital, Houston Methodist Hospital, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Street MC 3-3320, Houston, TX, 77030, USA. nahmed@bcm.edu.|Texas Children's Hospital, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA. nahmed@bcm.edu.|Departments of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA. nahmed@bcm.edu.
Nabil
N
Ahmed
D000293:Adolescent; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000378:metabolism / Q000472:pathogenicity; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000821:virology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism*; D007223:Infant; D008297:Male; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism*
C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa
CMV; GBM; Glioblastoma; IE1-72; Pediatric; pp65