Chimeric RNAs as potential biomarkers for tumor diagnosis

Zhou, Jian; Liao, Jo Shua; Zheng, Xue Xiu; Shen, Hai Hong

doi:10.5483/bmbrep.2012.45.3.133

Cited by 17 publications

(15 citation statements)

References 46 publications

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“…Next, we implemented additional filters, considering only predictions supported by 8 or more spanning reads and 5 or more split reads. Furthermore, we removed fusions involving ribosomal genes, mitochondrial genes and fusions between adjacent genes, as these could be caused by read-through or trans-splicing [50], [51] ( Figure 1.C ). …”

Section: Resultsmentioning

confidence: 99%

Comprehensive Analysis of Transcriptome Variation Uncovers Known and Novel Driver Events in T-Cell Acute Lymphoblastic Leukemia

et al. 2013

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RNA-seq is a promising technology to re-sequence protein coding genes for the identification of single nucleotide variants (SNV), while simultaneously obtaining information on structural variations and gene expression perturbations. We asked whether RNA-seq is suitable for the detection of driver mutations in T-cell acute lymphoblastic leukemia (T-ALL). These leukemias are caused by a combination of gene fusions, over-expression of transcription factors and cooperative point mutations in oncogenes and tumor suppressor genes. We analyzed 31 T-ALL patient samples and 18 T-ALL cell lines by high-coverage paired-end RNA-seq. First, we optimized the detection of SNVs in RNA-seq data by comparing the results with exome re-sequencing data. We identified known driver genes with recurrent protein altering variations, as well as several new candidates including H3F3A, PTK2B, and STAT5B. Next, we determined accurate gene expression levels from the RNA-seq data through normalizations and batch effect removal, and used these to classify patients into T-ALL subtypes. Finally, we detected gene fusions, of which several can explain the over-expression of key driver genes such as TLX1, PLAG1, LMO1, or NKX2-1; and others result in novel fusion transcripts encoding activated kinases (SSBP2-FER and TPM3-JAK2) or involving MLLT10. In conclusion, we present novel analysis pipelines for variant calling, variant filtering, and expression normalization on RNA-seq data, and successfully applied these for the detection of translocations, point mutations, INDELs, exon-skipping events, and expression perturbations in T-ALL.

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Section: Resultsmentioning

confidence: 99%

Comprehensive Analysis of Transcriptome Variation Uncovers Known and Novel Driver Events in T-Cell Acute Lymphoblastic Leukemia

et al. 2013

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“…(38) reported that similar to humans, rare events such as trans-splicing can still occur in rice. Trans-splicing is coined as a splicing event in which chimeric RNAs comprise exons from two or more different genes (38,43). Although this is thought to be a rare occurrence, the number of trans-splicings may be higher than expected.…”

Section: Regulation Of Splicing and Alternative Splicing In Humans Anmentioning

confidence: 99%

Splicing and alternative splicing in rice and humans

Zhiguo¹,

Wang²,

Zhou³

2013

BMB Reports

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Rice is a monocot gramineous crop, and one of the most important staple foods. Rice is considered a model species for most gramineous crops. Extensive research on rice has provided critical guidance for other crops, such as maize and wheat. In recent years, climate change and exacerbated soil degradation have resulted in a variety of abiotic stresses, such as greenhouse effects, lower temperatures, drought, floods, soil salinization and heavy metal pollution. As such, there is an extremely high demand for additional research, in order to address these negative factors. Studies have shown that the alternative splicing of many genes in rice is affected by stress conditions, suggesting that manipulation of the alternative splicing of specific genes may be an effective approach for rice to adapt to abiotic stress. With the advancement of microarrays, and more recently, next generation sequencing technology, several studies have shown that more than half of the genes in the rice genome undergo alternative splicing. This mini-review summarizes the latest progress in the research of splicing and alternative splicing in rice, compared to splicing in humans. Furthermore, we discuss how additional studies may change the landscape of investigation of rice functional genomics and genetically improved rice. [BMB Reports 2013; 46(9): 439-447]

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“…In the recent literature, these have been referred to as read-through gene fusions, transcription-induced chimeras, co-transcription of adjacent genes coupled with intergenic splicing (CoTIS), or conjoined genes. Several of these read-through fusion transcripts have been identified specifically in prostate cancer and are associated with cellular proliferation and disease progression [25–33]. Recurrent read-through transcripts have not yet been characterized in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Recurrent read-through fusion transcripts in breast cancer

Varley

Gertz

Roberts

et al. 2014

Breast Cancer Res Treat

153

192

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Read-through fusion transcripts that result from the splicing of two adjacent genes in the same coding orientation are a recently discovered type of chimeric RNA. We sought to determine if read-through fusion transcripts exist in breast cancer. We performed paired-end RNA-seq of 168 breast samples, including 28 breast cancer cell lines, 42 triple negative breast cancer primary tumors, 42 estrogen receptor positive (ER+) breast cancer primary tumors, and 56 non-malignant breast tissue samples. We analyzed the sequencing data to identify breast cancer associated read-through fusion transcripts. We discovered two recurrent read-through fusion transcripts that were identified in breast cancer cell lines, confirmed across breast cancer primary tumors, and were not detected in normal tissues (SCNN1A-TNFRSF1A and CTSD-IFITM10). Both fusion transcripts use canonical splice sites to join the last splice donor of the 5′ gene to the first splice acceptor of the 3′ gene, creating an in-frame fusion transcript. Western blots indicated that the fusion transcripts are translated into fusion proteins in breast cancer cells. Custom small interfering RNAs targeting the CTSD-IFITM10 fusion junction reduced expression of the fusion transcript and reduced breast cancer cell proliferation. Read-through fusion transcripts between adjacent genes with different biochemical functions represent a new type of recurrent molecular defect in breast cancer that warrant further investigation as potential biomarkers and therapeutic targets. Both breast cancer associated fusion transcripts identified in this study involve membrane proteins (SCNN1A-TNFRSF1A and CTSD-IFITM10), which raises the possibility that they could be breast cancer-specific cell surface markers.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-014-3019-2) contains supplementary material, which is available to authorized users.

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Chimeric RNAs as potential biomarkers for tumor diagnosis

Cited by 17 publications

References 46 publications

Comprehensive Analysis of Transcriptome Variation Uncovers Known and Novel Driver Events in T-Cell Acute Lymphoblastic Leukemia

Comprehensive Analysis of Transcriptome Variation Uncovers Known and Novel Driver Events in T-Cell Acute Lymphoblastic Leukemia

Splicing and alternative splicing in rice and humans

Recurrent read-through fusion transcripts in breast cancer

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