List of communications


Genetic characterization of glioblastoma stem cell heterogeneity

Francesca Orzan, Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060, Italy; Francesca de Bacco, Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060, Italy; Roberta Neggia, Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060, Italy; Gigliola Reato, Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060, Italy; Elena Casanova, Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060, Italy; Claudio Isella, Laboratory of Oncogenomics, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060, Italy; Enzo Medico, Laboratory of Oncogenomics, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060, Italy; Paola Porrati, Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, 20133, Italy; Serena Pellegatta, Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, 20133, Italy; Paolo Maria Comoglio, Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060, Italy; Gaetano Finocchiaro, Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, 20133, Italy; Carla Boccaccio, Laboratory of Cancer Stem Cell Research, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060, Italy


Glioblastoma (GBM) is highly heterogeneous. To investigate how GBM intertumoral heterogeneity is retained by its stem-like cells (GSCs), we performed a mutational and transcriptional analysis of 109 neurospheres (NS) derived from as many primary GBM. We found that two frequent genetic alterations often coexisting in GBM tissues, EGFR amplification and PTEN loss, are anticorrelated in NS, suggesting that EGFR and PTEN alterations mark distinct GSCs subclones, and can have interchangeable roles in driving tumor progression. Expression profiling showed that NS can be classified into the “classical”, “mesenchymal”, and “proneural” subtypes, or, even more robustly, in three spontaneous clusters partially overlapping with the above subtypes. Among the most differentially expressed genes, EGFR is highly enriched in the classical-proneural subtype/cluster 2; conversely, MET is anticorrelated with EGFR, and enriched in the mesenchymal subtype/cluster1-3. Analysis of an independent cohort of 70 GBM tissue samples showed that different tumors preferentially display either EGFR amplification/expression, or MET expression. Interestingly, in tumors coexpressing MET and EGFR, the two receptors mark different areas, indicating that genetically distinct subclones can coexist in the same tumor. These findings provide an overview of cancer stem cell heterogeneity in the general GBM population, and evidence for the presence of such heterogeneity in individual tumors.

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