Evidence map›Paper›PMID 25888189›Full record

ArticleBMC genomics2015

Functional characterization of BC039389-GATM and KLK4-KRSP1 chimeric read-through transcripts which are up-regulated in renal cell cancer.

Dorothee Pflueger, Christiane Mittmann, Silvia Dehler, Mark A Rubin, Holger Moch, Peter Schraml

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
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  5. Pattern recognition in the landscape of seemingly random chimeric transcripts.Computational and structural biotechnology journal · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Dorothee PfluegerInstitute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. dorothee.pflueger@usz.ch.
Christiane MittmannInstitute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. christiane.mittmann@usz.ch.
Silvia DehlerCancer Registry Zurich and Zug, University Hospital Zurich, Zurich, Switzerland. silvia.dehler@usz.ch.
Mark A RubinInstitute of Precision Medicine of Weill Cornell Medical College and New York-Presbyterian Hospital, New York, USA. rubinma@med.cornell.edu.
Holger MochInstitute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. holger.moch@usz.ch.
Peter SchramlInstitute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. peter.schraml@usz.ch.
University Hospital of Zurich · CHCornell University · USETH Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChimeric read-through RNAs are transcripts originating from two directly adjacent genes (<10 kb) on the same DNA strand. Although they are found in next-generation whole transcriptome sequencing (RNA-Seq) data on a regular basis, investigating them further has usually been refrained from. Therefore, their expression patterns or functions in general, and in oncogenesis in particular, are poorly understood.

resultsWe used paired-end RNA-Seq and a specifically designed computational data analysis pipeline (FusionSeq) to nominate read-through events in a small discovery set of renal cell carcinomas (RCC) and confirmed them in a larger validation cohort. 324 read-through events were called overall; 22/27 (81%) selected nominees passed validation with conventional PCR and were sequenced at the junction region. We frequently identified various isoforms of a given read-through event. 2/22 read-throughs were up-regulated: BC039389-GATM was higher expressed in RCC compared to benign adjacent kidney; KLK4-KRSP1 was expressed in 46/169 (27%) RCCs, but rarely in normal tissue. KLK4-KRSP1 expression was associated with worse clinical outcome in the patient cohort. In cell lines, both read-throughs influenced molecular mechanisms (i.e. target gene expression or migration/invasion) in a way that counteracted the effect of the respective parent transcript GATM or KLK4.

conclusionsOur data suggests that the up-regulation of read-through RNA chimeras in tumors is not random but causes regulatory effects on cellular mechanisms and may impact patient survival.

Indexed as

AdultAgedAged, 80 and overAmidinotransferasesBase SequenceCarcinoma, Renal CellCell LineCohort StudiesFemaleHigh-Throughput Nucleotide SequencingHumansKallikreinsKidney NeoplasmsMaleMiddle AgedMolecular Sequence DataAmidinotransferasesglycine amidinotransferasekallikrein 4KallikreinsOncogene Proteins, FusionRNA, MessengerRNA, Small Interfering

Identifiers

PMID25888189
PMCPMC4422297
OpenAlexW2075246537

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.