TY - JOUR
T1 - Selective cancer-germline gene expression in pediatric brain tumors
AU - Jacobs, Joannes F.M.
AU - Grauer, Oliver M.
AU - Brasseur, Francis
AU - Hoogerbrugge, Peter M.
AU - Wesseling, Pieter
AU - Gidding, Corrie E.
AU - Rakt, Mandy W.M.M.
AU - Figdor, Carl G.
AU - Coulie, Pierre G.
AU - Vries, I. Jolanda M.
AU - Adema, Gosse J.
N1 - Funding Information:
Acknowledgements The authors wish to thank Dr. B. Lethé for providing the reagents for LAGE-2/NY-ESO, GAGE-1,2,8 and ACTB quantitative PCR. Dr. E. De Plaen for the reagents for MAGEA2 and MAGEA12 quantitative PCR. Riki Willems for Immunohistochemistry with mAbs E978 (anti-NY-ESO-1), MA454 (anti-MAGE-A1), 57B (anti-MAGE-A4) and the IgG isotype negative control antibody on sections of medulloblastoma sample 1 (see Fig. 1 for relative mRNA expression). Original magnification 639. This sample was chosen because of the heterogeneous expression of the MAGE-A4 protein assistance with the pathology database. Thérèse Aerts and Madeleine Swinarska for technical assistance. This work was supported by grants from ‘‘The Quality of Life Gala’’ and ‘‘Stichting Vrienden van het Kinderoncologisch Centrum Zuid-Oost Nederland’’.
PY - 2008/7
Y1 - 2008/7
N2 - Cancer-germline genes (CGGs) code for immunogenic antigens that are present in various human tumors and can be targeted by immunotherapy. Their expression has been studied in a wide range of human tumors in adults. We measured the expression of 12 CGGs in pediatric brain tumors, to identify targets for therapeutic cancer vaccines. Real Time PCR was used to quantify the expression of genes MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MAGE-C2, NY-ESO-1 and GAGE-1,2, 8 in 50 pediatric brain tumors of different histological subtypes. Protein expression was examined with immunohistochemistry. Fifty-five percent of the medulloblastomas (n = 11), 86% of the ependymomas (n = 7), 40% of the choroid plexus tumors (n = 5) and 67% of astrocytic tumors (n = 27) expressed one or more CGGs. Immunohistochemical analysis confirmed qPCR results. With exception of a minority of tumors, the overall level of CGG expression in pediatric brain tumors was low. We observed a high expression of at least one CGG in 32% of the samples. CGG-encoded antigens are therefore suitable targets in a very selected group of pediatric patients with a brain tumor. Interestingly, glioblastomas from adult patients expressed CGGs more often and at significantly higher levels compared to pediatric glioblastomas. This observation is in line with the notion that pediatric and adult glioblastomas develop along different genetic pathways.
AB - Cancer-germline genes (CGGs) code for immunogenic antigens that are present in various human tumors and can be targeted by immunotherapy. Their expression has been studied in a wide range of human tumors in adults. We measured the expression of 12 CGGs in pediatric brain tumors, to identify targets for therapeutic cancer vaccines. Real Time PCR was used to quantify the expression of genes MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MAGE-C2, NY-ESO-1 and GAGE-1,2, 8 in 50 pediatric brain tumors of different histological subtypes. Protein expression was examined with immunohistochemistry. Fifty-five percent of the medulloblastomas (n = 11), 86% of the ependymomas (n = 7), 40% of the choroid plexus tumors (n = 5) and 67% of astrocytic tumors (n = 27) expressed one or more CGGs. Immunohistochemical analysis confirmed qPCR results. With exception of a minority of tumors, the overall level of CGG expression in pediatric brain tumors was low. We observed a high expression of at least one CGG in 32% of the samples. CGG-encoded antigens are therefore suitable targets in a very selected group of pediatric patients with a brain tumor. Interestingly, glioblastomas from adult patients expressed CGGs more often and at significantly higher levels compared to pediatric glioblastomas. This observation is in line with the notion that pediatric and adult glioblastomas develop along different genetic pathways.
KW - Brain tumor
KW - Immune target
KW - MAGE
KW - NY-ESO-1
KW - Pediatrics
KW - qPCR
UR - http://www.scopus.com/inward/record.url?scp=44649146376&partnerID=8YFLogxK
U2 - 10.1007/s11060-008-9577-6
DO - 10.1007/s11060-008-9577-6
M3 - Article
C2 - 18398575
AN - SCOPUS:44649146376
SN - 0167-594X
VL - 88
SP - 273
EP - 280
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 3
ER -