E-GEOD-12992 - Beta-catenin status in pediatric medulloblastomas

Status
Released on 2 February 2009, last updated on 27 June 2012
Organism
Homo sapiens
Samples (40)
Array (1)
Protocols (6)
Description
Medulloblastoma is the most frequent malignant pediatric brain tumor. Considerable efforts are dedicated to identify markers that help to refine treatment strategies. The activation of the Wnt/beta-catenin pathway occurs in 10-15% of medulloblastomas and has been recently described as a marker for favorable patient outcome. We report a series of 72 pediatric medulloblastomas evaluated for beta-catenin immunostaining, CTNNB1 mutations, and studied by comparative genomic hybridization. Gene expression profiles were also available in a subset of 40 cases. Immunostaining of beta-catenin showed extensive nuclear staining (>50% of the tumor cells) in 6 cases and focal nuclear staining (<10% of cells) in 3 cases. The other cases exhibited either a signal strictly limited to the cytoplasm (58 cases) or were negative (5 cases). CTNNB1 mutations were detected in all beta-catenin extensively nucleopositive cases. The expression profiles of these cases documented a strong activation of the Wnt/beta-catenin pathway. Remarkably, 5 out of these 6 tumors showed a complete loss of chromosome 6. In contrast, cases with focal nuclear beta-catenin staining, as well as tumors with negative or cytoplasmic staining, never demonstrated CTNNB1 mutation, Wnt/beta-catenin pathway activation or chromosome 6 loss. Patients with extensive nuclear staining were significantly older at diagnosis and were in continuous complete remission after a mean follow-up of 75.7 months (range 27.5-121.2) from diagnosis. All three patients with a focal nuclear staining of beta-catenin died within 36 months from diagnosis. Altogether, these data confirm and extend previous observations that CTNNB1-mutated tumors represent a distinct molecular subgroup of medulloblastomas with favorable outcome, indicating that therapy de-escalation should be considered. Yet, international consensus on the definition criteria of this distinct medulloblastoma subgroup should be achieved. A series of 72 pediatric medulloblastoma tumors has been studied at the genomic level (array-CGH), screened for CTNNB1 mutations and beta-catenin expression (immunohistochemistry). A subset of 40 tumor samples has been analyzed at the RNA expression level (Affymetrix HG U133 Plus 2.0). Correlations between the genomic data, the expression data, the mutational screening, the pathological classification and clinical data is presented in the study. note: aCGH data not submitted to GEO
Experiment type
transcription profiling by array 
Contacts
Olivier Delattre <olivier.delattre@curie.fr>, Arielle Lellouch-Tubiana, Christine Haberler, Danielle Bours, Elodie Manie, Emmanuel Barillot, Francois Doz, Isabelle Janoueix-Lerosey, Jacques Grill, Marie-Anne Raquin, Pascale Varlet, Patricia Legoix, Sabrina Carpentier, Sarah Fattet, Severine Lair, Stephanie Puget
Citation
Beta-catenin status in paediatric medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics. Fattet S, Haberler C, Legoix P, Varlet P, Lellouch-Tubiana A, Lair S, Manie E, Raquin MA, Bours D, Carpentier S, Barillot E, Grill J, Doz F, Puget S, Janoueix-Lerosey I, Delattre O. , Europe PMC 19197950
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-12992.idf.txt
Sample and data relationshipE-GEOD-12992.sdrf.txt
Raw data (3)E-GEOD-12992.raw.1.zip, E-GEOD-12992.raw.2.zip, E-GEOD-12992.raw.3.zip
Processed data (1)E-GEOD-12992.processed.1.zip
Array designA-AFFY-44.adf.txt
R ExpressionSetE-GEOD-12992.eSet.r
Links