Expression of neurogenic basic helix-loop-helix genes in primitive neuroectodermal tumors.
The basic helix-loop-helix (bHLH) class of transcription factors plays a pivotal role in tissue-specific determination and differentiation. Moreover, dysregulated expression or loss of function of these factors contributes to leukemogenesis and solid tumor development. Neurogenesis is regulated by genes of the NEUROD/atonal and ACHAETE SCUTE families. We analyzed expression of human NEUROD1, NEUROD2, NEUROD3, and ACHAETE SCUTE 1 (HASH1) in cerebellar and cerebral primitive neuroectodermal tumors (PNETs), gliomas, and cell lines derived from a variety of neuroectodermal tumors by Northern analysis and in situ hybridization. NEUROD1 was expressed in each of the 12 medulloblastoma specimens, whereas NEUROD2 and NEUROD3/neurogenin were expressed in partly overlapping subsets of medulloblastomas. All of the tumors that presented with distant metastases expressed NEUROD3. The only other NEUROD3-positive tumor progressed early in treatment. Human ACHAETE SCUTE homologue (HASH1) was not expressed in medulloblastomas (infratentorial PNETs) but was expressed in three of five supratentorial PNETs. Neuroectodermal tumor cell lines derived from other sites (e.g., neuroblastoma and retinoblastoma) expressed NeuroD and ACHAETE SCUTE family members. No NEUROD message was detected in glial tumors or cell lines. Neurogenic bHLH transcription factor expression patterns suggest that specific family members may contribute to or reflect biological differences that arise during malignant transformation.
Rostomily
R C
RC
Department of Neurological Surgery, The University of Washington School of Medicine, Seattle 98195, USA.
Bermingham-McDonogh
O
O
Berger
M S
MS
Tapscott
S J
SJ
Reh
T A
TA
Olson
J M
JM
D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000378:metabolism; D002648:Child; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors