Transcriptomic but not genomic variability confers phenotype of breast cancer stem cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA477551 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7414370_1.fastq.gz | Fastqsanger.gz | |||
| SRR7414370_2.fastq.gz | Fastqsanger.gz | |||
| SRR7414371_1.fastq.gz | Fastqsanger.gz | |||
| SRR7414371_2.fastq.gz | Fastqsanger.gz | |||
| SRR7414372_1.fastq.gz | Fastqsanger.gz |
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Project description:Background: Breast cancer stem cells (BCSCs) are considered responsible for cancer relapse and drug-resistance. Understanding the identity of BCSCs may open new avenues in breast cancer therapy. Although several discoveries have been made on BCSCs characterization, the factors critical to BCSCs is largely unclear. This study was aimed to determine whether genomic mutation contributes to the acquisition of cancer stem-like phenotype, and to investigate the genetic and transcriptional features of BCSCs. Methods: We detected the potential mutation hotspot regions by using whole genome sequencing on parental cancer cells and derived serial-generation spheroids in increasing order of BCSC frequency, and then performed target deep DNA sequencing in the level of bulk-cell and single-cell. To identify the transcriptional program associated with BCSCs, bulk-cell and single-cell RNA sequencing were performed. Results: By analyzing whole genome sequencing of bulk cells, potential BCSCs associated mutation hotspot regions were detected. Validation by target deep sequencing, in both bulk-cell and single-cell levels, revealed no genetic changes specifically associated with BCSC phenotype. Moreover, single-cell RNA sequencing showed that cancer cells display profound transcriptional variability at the single-cell level that predicts BCSC features. Notably, this transcriptomic variability is enriched in transcription of a number of genes, revealed as BCSC markers. Individuals with breast cancer in a high-risk recurrence group exhibited higher expression of these transcriptomic variabilities, highlighting their clinical significance. Conclusions: Transcriptional variability, not genetic mutations, distinguish BCSCs from non-BCSCs. The identified BCSCs markers can become novel targets for BCSCs.
2018-10-12 | GSE116180 | GEO
Project description:BackgroundBreast cancer stem cells (BCSCs) are considered responsible for cancer relapse and drug resistance. Understanding the identity of BCSCs may open new avenues in breast cancer therapy. Although several discoveries have been made on BCSC characterization, the factors critical to the origination of BCSCs are largely unclear. This study aimed to determine whether genomic mutations contribute to the acquisition of cancer stem-like phenotype and to investigate the genetic and transcriptional features of BCSCs.MethodsWe detected potential BCSC phenotype-associated mutation hotspot regions by using whole-genome sequencing on parental cancer cells and derived serial-generation spheres in increasing order of BCSC frequency, and then performed target deep DNA sequencing at bulk-cell and single-cell levels. To identify the transcriptional program associated with BCSCs, bulk-cell and single-cell RNA sequencing was performed.ResultsBy using whole-genome sequencing of bulk cells, potential BCSC phenotype-associated mutation hotspot regions were detected. Validation by target deep DNA sequencing, at both bulk-cell and single-cell levels, revealed no genetic changes specifically associated with BCSC phenotype. Moreover, single-cell RNA sequencing showed profound transcriptomic variability in cancer cells at the single-cell level that predicted BCSC features. Notably, this transcriptomic variability was enriched during the transcription of 74 genes, revealed as BCSC markers. Breast cancer patients with a high risk of relapse exhibited higher expression levels of these BCSC markers than those with a low risk of relapse, thereby highlighting the clinical significance of predicting breast cancer prognosis with these BCSC markers.ConclusionsTranscriptomic variability, not genetic mutations, distinguishes BCSCs from non-BCSCs. The identified 74 BCSC markers have the potential of becoming novel targets for breast cancer therapy.
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