Genomics

Dataset Information

45

Neuroblastoma cells undergo transcriptomic alterations during dissemination into the bone marrow and subsequent tumor progression


ABSTRACT: Background: Neuroblastoma is the most common extracranial solid tumor in childhood. The vast majority of stage M patients present with disseminated tumor cells (DTCs) in the bone marrow (BM). Although these cells represent a major obstacle in the treatment of neuroblastoma patients, their transcriptomic profile was not intensively analyzed so far. Results: RNA-Seq of stage M primary tumors, enriched BM-derived DTCs and the corresponding non-tumor mononuclear cells (MNCs) revealed that DTCs largely retained the gene expression signature of tumors. However, we identified 322 genes that were differentially expressed (q < 0.001, |log2FC|>2). Particularly genes encoded by mitochondrial DNA were highly up-regulated in DTCs, whereas e.g. genes involved in angiogenesis were down-regulated. Furthermore, 224 genes were highly expressed in DTCs and only slightly, if at all, in MNCs (q < 8x10-75 log2FC > 6). Interestingly, we found that the gene expression profiles of diagnostic DTCs largely resembled those of relapse DTCs with only 113 differentially expressed genes under relaxed cut-offs (q < 0.01, |log2FC| > 0.5). Notably, relapse DTCs showed a positional enrichment of 31 down-regulated genes encoded by chromosome 19, including five tumor suppressor genes (SIRT6, PUMA, STK11, CADM4 and GLTSCR2). Conclusion: This first RNA-Seq analysis of DTCs from neuroblastoma patients revealed their unique expression profile in comparison to the corresponding MNCs and tumor samples, and, interestingly, also expression differences between diagnostic and relapse DTCs preferentially affecting chromosome 19. As these alterations might be associated with treatment failure and disease relapse, they should be considered for further functional studies. Overall design: Tumor (n=16), bone marrow-derived disseminated tumor cells (n=42) and corresponding bone marrow-derived non-tumor cells (n=28) of stage M neuroblastoma patients were used for RNA-Seq

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Fikret Rifatbegovic  

PROVIDER: GSE94035 | GEO | 2017-08-21

SECONDARY ACCESSION(S): PRJNA368627

REPOSITORIES: GEO

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Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression.

Rifatbegovic Fikret F   Frech Christian C   Abbasi M Reza MR   Taschner-Mandl Sabine S   Weiss Tamara T   Schmidt Wolfgang M WM   Schmidt Iris I   Ladenstein Ruth R   Ambros Inge M IM   Ambros Peter F PF  

International journal of cancer 20171004 2


Neuroblastoma is the most common extracranial solid tumor in childhood. The vast majority of metastatic (M) stage patients present with disseminated tumor cells (DTCs) in the bone marrow (BM) at diagnosis and relapse. Although these cells represent a major obstacle in the treatment of neuroblastoma patients, insights into their expression profile remained elusive. The present RNA-Seq study of stage 4/M primary tumors, enriched BM-derived diagnostic and relapse DTCs, as well as the corresponding  ...[more]

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