Upregulation of SOX2, NOTCH1, and ID1 in supratentorial primitive neuroectodermal tumors: a distinct differentiation pattern from that of medulloblastomas.
OBJECTIVE
Supratentorial primitive neuroectodermal tumor (PNET) and medulloblastoma are highly malignant embryonal brain tumors. They share morphological similarities, but differ in their differentiation patterns and global gene expression. The authors compared the expression of specific genes involved in neuroglial differentiation in supratentorial PNETs and medulloblastomas to define the distinct characters of these tumors.


METHODS
The mRNA expression of 8 genes (SOX2, NOTCH1, ID1, ASCL-1, NEUROD1, NEUROG1, NEUROG2, and NRG1) was evaluated in 25 embryonal tumors (12 supratentorial PNETs and 13 medulloblastomas) by quantitative real-time polymerase chain reaction. The expression levels of the transcripts of these genes were compared between the tumor groups. Activation of the JAK/STAT3 pathway was assessed by immunoblotting. Relative expression levels of STAT3 and phosphorylated STAT3 proteins were compared.


RESULTS
Supratentorial PNETs expressed significantly higher levels of SOX2, NOTCH1, ID1, and ASCL-1 transcripts, whereas the transcription of proneural basic helix-loop-helix factors, NEUROD1, NEUROG1 (significantly), and NEUROG2 (not significantly) was upregulated in medulloblastomas. The proportion of phosphorylated STAT3alpha relative to STAT3alpha was significantly greater in supratentorial PNETs than in medulloblastomas, indicating activation of the JAK/STAT3 pathway in supratentorial PNETs.


CONCLUSIONS
These results indicate that supratentorial PNET predominantly has glial features and medulloblastoma largely follows a neuronal differentiation pattern. These divergent differentiation patterns may be related to the location and origin of each tumor.
Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, 101 Daehangno, Jongno-gu, Seoul, 110-744, Republic of Korea.
Ji Hoon
JH
Phi
Jin Hyun
JH
Kim
Kyoung Mi
KM
Eun
Kyu-Chang
KC
Wang
Ki Ho
KH
Park
Seung Ah
SA
Choi
Young Yim
YY
Kim
Sung-Hye
SH
Park
Byung-Kyu
BK
Cho
Seung-Ki
SK
Kim
D000293:Adolescent; D000328:Adult; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics*; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000473:pathology; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics* / Q000473:pathology; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics*; D015173:Supratentorial Neoplasms / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*
C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; C497761:NOTCH1 protein, human; D012333:RNA, Messenger; D051881:Receptor, Notch1; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human