ArticleOncogene2005
A mutation-created novel intra-exonic pre-mRNA splice site causes constitutive activation of KIT in human gastrointestinal stromal tumors.
Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
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.
Who cites it
18 citing papers in PubMed, 45 citations in OpenAlex.
- Identification and analysis of short indels inducing exon extension/shrinkage events.FEBS open bio · 2024Article
- Genomic Characterization of Prostatic Basal Cell Carcinoma.The American journal of pathology · 2023Article
- Splice variants of RAS-translational significance.Cancer metastasis reviews · 2020Review
- A novel splice site indel alteration in the EIF2AK3 gene is responsible for the first cases of Wolcott-Rallison syndrome in Hungary.BMC medical genetics · 2020Article
- Alternative tumour-specific antigens.Nature reviews. Cancer · 2019Review
- A novel 40kDa N-terminal truncated carboxypeptidase E splice variant: cloning, cDNA sequence analysis and role in regulation of metastatic genes in human cancers.Genes & cancer · 2019Article
- Systematic Analysis of Splice-Site-Creating Mutations in Cancer.Cell reports · 2018Article
- Addiction to multiple oncogenes can be exploited to prevent the emergence of therapeutic resistance.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Splice variants of zinc finger protein 695 mRNA associated to ovarian cancer.Journal of ovarian research · 2013Article
- Alternative splicing in oncogenic kinases: from physiological functions to cancer.Journal of nucleic acids · 2012Article
- The pathobiology of splicing.The Journal of pathology · 2010Review
- hnRNP A2 regulates alternative mRNA splicing of TP53INP2 to control invasive cell migration.Cancer research · 2009Article
- Alternative splicing of pre-mRNA in cancer: focus on G protein-coupled peptide hormone receptors.The American journal of pathology · 2009Review
- Alternative splicing and tumor progression.Current genomics · 2008Article
- A comprehensive analysis of prognostic signatures reveals the high predictive capacity of the proliferation, immune response and RNA splicing modules in breast cancer.Breast cancer research : BCR · 2008Article
- Pre-apoptotic response to therapeutic DNA damage involves protein modulation of Mcl-1, Hdm2 and Flt3 in acute myeloid leukemia cells.Molecular cancer · 2007Article
- Microfluidic deletion/insertion analysis for rapid screening of KIT and PDGFRA mutations in CD117-positive gastrointestinal stromal tumors: diagnostic applications and report of a new KIT mutation.The Journal of molecular diagnostics : JMD · 2007Article
- Aberrant 3' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.Nucleic acids research · 2006Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We report a new mechanism of aberrant pre-mRNA splicing resulting in constitutive activation of a mis-spliced oncoprotein (KIT) leading to malignancy (gastrointestinal stromal tumor) in contrast to loss of function of mis-spliced proteins resulting in diverse human diseases in the literature. The mechanisms of three consecutive molecular events, deletion of noncoding and coding regions encompassing the 3' authentic splice site, creation of a novel intra-exonic pre-mRNA 3' splice acceptor site leading to in-frame loss of 27 nucleotides (nine amino acids; Lys550-Lys558), and the mechanism of constitutive activation of the mis-spliced KIT are elucidated. Loss of a peptide in a critical location unleashed the protein from autoinhibition (as evidenced by three-dimensional structural analysis), causing KIT to become constitutively activated and resulting in the GIST phenotype. We also demonstrated that only one of the following two exonic splicing enhancers is sufficient for inclusion of the KIT exon 11 in vivo: AACCCATGT (nucleotides 2-10 from the 5' end, which are recognized by SC35, SRp55, and SF2/ASF) or GGTTGTTGAGG (nucleotides 27-37 from the 5' end, which are recognized by SC35 and SRp55), suggestive of exonic enhancer redundancy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.