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This Article Full Text Full Text (PDF) All Versions of this Article: 9/3/298    most recent 15228517-2007-014v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Salsano, E. Articles by Finocchiaro, G. Search for Related Content PubMed PubMed Citation

Expression of the neurogenic basic helix-loop-helix transcription factor NEUROG1 identifies a subgroup of medulloblastomas not expressing ATOH1

Unit of Experimental Neuro-Oncology (E.S., L.L., G.F.) and Division of Neuropathology (E.M., B.P.), "Carlo Besta" Neurological Institute Foundation, 20133 Milan; San Raffaele Scientific Institute, 20132 Milan (L.C., G.G.C.); and Department of Neurosciences, University of Turin, 10126 Turin (M.T.G.); Italy

Address correspondence to Ettore Salsano, Unit of Experimental Neuro-Oncology, "Carlo Besta" Neurological Institute Foundation, via Celoria 11, 20133 Milan, Italy (ettore.salsano{at}istituto-besta.it).

To gain insight into the lineage of origin of medulloblastomas, the mRNA expression of NEUROG1, a gene encoding a proneural transcription factor transiently detected during nervous system development, was investigated in 27 human medulloblastomas characterized for mRNA expression of ATOH1, a marker of cerebellar granule precursors and corresponding medulloblastomas. Expression of Ngn1, the mouse homolog of NEUROG1, was also analyzed in the mouse cerebellar primordium. In addition, we studied mRNA expression of GLI1 as a marker of the SHH pathway activation, and nuclear ß-catenin staining, ß-catenin mutations, and mRNA expression of MYC as indicators of the WNT pathway status. In 15 cases, we also examined expression of OTX2, a transcription factor recently indicated as a positive marker of medulloblastomas originating from cerebellar granule precursors. The mRNA expression of NEUROG1 and Ngn1 was selectively found in medulloblastomas not expressing ATOH1 and in progenitors of the cerebellar ventricular zone, respectively. GLI1 transcript was expressed in medulloblastomas with ATOH1 transcript, whereas high levels of MYC transcript were unrelated to NEUROG1 or ATOH1 expression. No clear association between MYC overexpression and nuclear ß-catenin staining was found. Finally, OTX2 mRNA was expressed in all medulloblastomas with NEUROG1 transcript, but also in a subset of these malignancies with ATOH1 transcript. These observations may help to define the lineage of origin of medulloblastomas, and support a role for ATOH1 and NEUROG1 in the classification of these malignancies.

Key Words: ATOH1 (MATH-1) • cerebellum • GLI1 • medulloblastoma • MYC • NEUROG1 (neurogenin-1) • OTX2

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