Unknown,Transcriptomics,Genomics,Proteomics

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Genome profiling by comparative genomic hybridization (CGH) in pediatric osteosarcoma

ABSTRACT: In some types of cancer, telomere length is maintained by the Alternative Lengthening of Telomeres (ALT) mechanism. We characterized a series of high-grade osteosarcomas from 22 non-metastatic and non-pre-treated pediatric patients. Using the presence of circular partially single-stranded extrachromosomal C-rich telomeric repeat sequences (C-Circles) as an ALT marker, we found that 16 of the 22 high-grade osteosarcomas were ALT-positive. In order to find copy number alterations associated with ALT mechanims, we used comparative genomic hybridization (CGH).

ORGANISM(S): Homo sapiens

SUBMITTER: Arnaud Guille

PROVIDER: E-MTAB-11747 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background Primitive brain tumors are the first cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined. Methodology/Principal findings Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). The vast majority (10/12) of high-grade glioma-derived oncospheres sustained long-term self-renewal numbers akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumor types. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P=0.05, chi-square test). TSCs shared a complex molecular profile combining embryonic stem cell markers with elements controlling neural stem cell properties and epithelio-mesenchymal transitions. They were radio- and chemoresistant and formed aggressive tumors after intracerebral grafting. Survival analysis of the cohort showed an association between isolation of TSCs with long-term self-renewal abilities and a patients higher mortality rate (P = 0.022, log-rank test). Patients bearing cells with limited self-renewal properties constituted an intermediate group of survival but which did not reach statistical significance. Conclusions/Significance In brain tumors affecting adult patients, TSC have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors.

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Genome profiling by comparative genomic hybridization (CGH) in pediatric osteosarcoma

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