Expression of the neurogenic basic helix-loop-helix transcription factor NEUROG1 identifies a subgroup of medulloblastomas not expressing ATOH1.
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 beta-catenin staining, beta-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 beta-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.
Salsano
Ettore
E
Unit of Experimental Neuro-Oncology, Carlo Besta Neurological Institute Foundation, via Celoria 11, 20133 Milan, Italy. ettore.salsano@istituto-besta.it
Croci
Laura
L
Maderna
Emanuela
E
Lupo
Linda
L
Pollo
Bianca
B
Giordana
Maria Teresa
MT
Consalez
G Giacomo
GG
Finocchiaro
Gaetano
G
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis*; D019070:Cell Lineage / Q000502:physiology*; D002528:Cerebellar Neoplasms / Q000145:classification / Q000378:metabolism*; D002531:Cerebellum / Q000196:embryology; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008527:Medulloblastoma / Q000145:classification / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D051857:Otx Transcription Factors; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis; D000071676:Zinc Finger Protein GLI1; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D051176:beta Catenin; C500942:ATOH1 protein, human; C400551:GLI1 protein, human; C105389:NEUROG1 protein, human; C497659:OTX2 protein, human