Long-range Transcriptome Sequencing Reveals Cancer Cell Growth Regulatory Chimeric mRNA

Plebani, Roberto; Oliver, Gavin R.; Trerotola, Marco; Guerra, Emanuela; Cantanelli, Pamela; Apicella, L.; Emerson, Andrew; Albiero, Alessandro; Harkin, Paul; Kennedy, Richard D.; Alberti, Saverio

doi:10.1593/neo.121342

Cited by 19 publications

(14 citation statements)

References 56 publications

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“…In addition to CLTC-VMP1 fusion, we also found an intra-chromosomal fusion event (JCV=68.52) involving CTBS-GNG5 genes in a tumor sample ( Supplementary Table 4 ). The same fusion is reported previously in multiple cancer cell lines and primary tissues [ 24 ] but its functional consequences are currently not understood.…”

Section: Resultssupporting

confidence: 67%

Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx

et al. 2015

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Laryngo-pharyngeal squamous cell carcinomas are one of the most common head and neck cancers. Despite the presence of a large body of information, molecular biomarkers are not currently used in the diagnosis, treatment and management of patients for this group of cancer. Here, we have profiled expression of genes and microRNAs of larynx and hypopharynx tumors using high-throughput sequencing experiments. We found that matrix metalloproteinases along with SCEL, CRNN, KRT4, SPINK5, and TGM3 among others have significantly altered expression in these tumors. Alongside gene expression, the microRNAs hsa-miR-139, hsa-miR-203 and the hsa-miR-424/503 cluster have aberrant expression in these cancers. Using target genes for these microRNAs, we found the involvement of pathways linked to cell cycle, p53 signaling, and viral carcinogenesis significant (P-values 10−13, 10−9 and 10−7 respectively). Finally, using an ensemble machine-learning tool, we discovered a unique 8-gene signature for this group of cancers that differentiates the group from the other tumor subsites of head and neck region. We investigated the role of promoter methylation in one of these genes, WIF1, and found no correlation between DNA methylation and down-regulation of WIF1. We validated our findings of gene expression, 8-gene signature and promoter methylation using q-PCR, data from TCGA and q-MSP respectively.Data presented in this manuscript has been submitted to the NCBI Geo database with the accession number GSE67994.

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Section: Resultssupporting

confidence: 67%

Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx

et al. 2015

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“…Using RT-PCR, we could detect CTBS-GNG5 in nearly all of the tissues and cell lines we tested (Figure 5B ). It was also found by RNA-Sequencing of cancer cells and seems to be conserved in mouse ( 30 – 32 ). CTBS encodes chitobiase; GNG5 encodes the di- N - acetyl-binding and guanine-nucleotide-binding proteins.…”

Section: Resultsmentioning

confidence: 75%

Recurrent chimeric fusion RNAs in non-cancer tissues and cells

Babiceanu¹,

Qin²,

Xie³

et al. 2016

Nucleic Acids Res

160

213

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Gene fusions and their products (RNA and protein) were once thought to be unique features to cancer. However, chimeric RNAs can also be found in normal cells. Here, we performed, curated and analyzed nearly 300 RNA-Seq libraries covering 30 different non-neoplastic human tissues and cells as well as 15 mouse tissues. A large number of fusion transcripts were found. Most fusions were detected only once, while 291 were seen in more than one sample. We focused on the recurrent fusions and performed RNA and protein level validations on a subset. We characterized these fusions based on various features of the fusions, and their parental genes. They tend to be expressed at higher levels relative to their parental genes than the non-recurrent ones. Over half of the recurrent fusions involve neighboring genes transcribing in the same direction. A few sequence motifs were found enriched close to the fusion junction sites. We performed functional analyses on a few widely expressed fusions, and found that silencing them resulted in dramatic reduction in normal cell growth and/or motility. Most chimeras use canonical splicing sites, thus are likely products of ‘intergenic splicing’. We also explored the implications of these non-pathological fusions in cancer and in evolution.

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“…Proof of non-random expression of such fusion transcripts in normal tissue types with translation into chimeric proteins have been described [ 15 ]. Several reports have shown that such fusion transcripts have an impact on cancer biology, by regulating both replication and cell growth in cancer [ 16 – 19 ]. Chimeric mRNAs expressed in normal cells are sometimes overexpressed in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Novel RNA variants in colorectal cancers

et al. 2015

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With an annual estimated incidence of 1.4 million, and a five-year survival rate of 60%, colorectal cancer (CRC) is a major clinical burden. To identify novel RNA variants in CRC, we analyzed exon-level microarray expression data from a cohort of 202 CRCs. We nominated 25 genes with increased expression of their 3′ parts in at least one cancer sample each. To efficiently investigate underlying transcript structures, we developed an approach using rapid amplification of cDNA ends followed by high throughput sequencing (RACE-seq). RACE products from the targeted genes in 23 CRC samples were pooled together and sequenced. We identified VWA2-TCF7L2, DHX35-BPIFA2 and CASZ1-MASP2 as private fusion events, and novel transcript structures for 17 of the 23 other candidate genes. The high-throughput approach facilitated identification of CRC specific RNA variants. These include a recurrent read-through fusion transcript between KLK8 and KLK7, and a splice variant of S100A2. Both of these were overrepresented in CRC tissue and cell lines from external RNA-seq datasets.

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Long-range Transcriptome Sequencing Reveals Cancer Cell Growth Regulatory Chimeric mRNA

Cited by 19 publications

References 56 publications

Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx

Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx

Recurrent chimeric fusion RNAs in non-cancer tissues and cells

Novel RNA variants in colorectal cancers

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