Expression of MATH1, a marker of cerebellar granule cell progenitors, identifies different medulloblastoma sub-types.
In order to look for genetic markers helpful for the biological risk stratification of medulloblastomas (MBs) we assayed by real-time PCR expression levels of the following genes: MATH1, encoding a critical transcription factor for the differentiation of cerebellar granular cells (CGCs); PEDF, that encodes a trophic factor for CGCs and is located in a region of frequent allelic imbalance in MBs; and BIRC5, encoding the antiapoptotic protein survivin, usually overexpressed in malignancies. Expression levels of TRKC, higher in MBs with a more favorable prognosis, were also studied. Twenty-three patients were considered: MATH1 expression was strong in 14/23 and undetectable in the others. PEDF was up-regulated in 8/23, TRKC in 9/23, and BIRC5 in 23/23. MATH1 expression was significantly correlated with adult age (p < 0.0001), tumor location in hemispheres rather than the vermis (p < 0.0004), and PEDF and TRKC up-regulation (p < 0.008 and p < 0.04, respectively). During development MATH1 is selectively expressed in the external germinal layer (EGL) of the cerebellum. Thus, MATH1 expression identifies a subgroup of MBs that derive from the EGL and arise during adult age into cerebellar hemispheres. MATH1 mRNA-positive MBs express high levels of PEDF and show a trend towards longer survival, in agreement with increased expression of TRKC. BIRC5 expression, which is strong in all MBs and absent in normal cerebellum, lacks any prognostic value but could be explored for selective targeting of therapeutic factors to MBs.
Department of Experimental Neurosciences and Diagnostics, Unit of Experimental Neuro-Oncology and Gene Therapy, via Celoria 11, 20133 Milano, Italy.
Ettore
E
Salsano
Bianca
B
Pollo
Marica
M
Eoli
Maria Teresa
MT
Giordana
Gaetano
G
Finocchiaro
D000293:Adolescent; D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008527:Medulloblastoma / Q000145:classification* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D000077022:Survivin; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D005136:Eye Proteins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D020812:Receptor, trkC; D015843:Serpins; D000077022:Survivin; D014157:Transcription Factors; D000099174:Pigment Epithelium-Derived Factor; C500943:Atoh1 protein, mouse; C107489:BIRC5 protein, human