ArticleCancer research2009
An A13 repeat within the 3'-untranslated region of epidermal growth factor receptor (EGFR) is frequently mutated in microsatellite instability colon cancers and is associated with increased EGFR expression.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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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.
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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.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
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- CYpHER: catalytic extracellular targeted protein degradation with high potency and durable effect.Nature communications · 2024Article
- Potent therapeutic strategy in gastric cancer with microsatellite instability-high and/or deficient mismatch repair.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Review
- Detecting microsatellite instability by length comparison of microsatellites in the 3' untranslated region with RNA-seq.Briefings in bioinformatics · 2024Article
- Multi-level functional genomics reveals molecular and cellular oncogenicity of patient-based 3' untranslated region mutations.Cell reports · 2023Article
- Epidermal growth factor receptor intron 1 polymorphism and microsatellite instability in sporadic colorectal cancer.Oncology letters · 2021Article
- Y-box binding protein 1 acts as a negative regulator of stearoyl CoA desaturase 1 in clear cell renal cell carcinoma.Oncology letters · 2020Article
- Epidermal growth factor receptor intron-1 CA repeat polymorphism on protein expression and clinical outcome in Taiwanese oral squamous cell carcinoma.Scientific reports · 2017Article
- Regulation of mismatch repair by histone code and posttranslational modifications in eukaryotic cells.DNA repair · 2016Review
- Instability of a dinucleotide repeat in the 3'-untranslated region (UTR) of the microsomal prostaglandin E synthase-1 (mPGES-1) gene in microsatellite instability-high (MSI-H) colorectal carcinoma.Molecular oncology · 2015Article
- Phosphorylation of PCNA by EGFR inhibits mismatch repair and promotes misincorporation during DNA synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Causes and consequences of microsatellite instability in gastric carcinogenesis.World journal of gastroenterology · 2014Review
- Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for patients with resected colorectal cancer liver metastases.British journal of cancer · 2014Article
- Prospective study of EGFR intron 1 (CA)n repeats variants as predictors of benefit from cetuximab and irinotecan in chemo-refractory metastatic colorectal cancer (mCRC) patients.The pharmacogenomics journal · 2014Article
- Oncogenic mutations and microsatellite instability phenotype predict specific anatomical subsite in colorectal cancer patients.European journal of human genetics : EJHG · 2013Article
- The landscape of microsatellite instability in colorectal and endometrial cancer genomes.Cell · 2013Article
- Comprehensive genome- and transcriptome-wide analyses of mutations associated with microsatellite instability in Korean gastric cancers.Genome research · 2013Article
- Genetic variations of the A13/A14 repeat located within the EGFR 3' untranslated region have no oncogenic effect in patients with colorectal cancer.BMC cancer · 2013Article
- Somatic deletions of the polyA tract in the 3' untranslated region of epidermal growth factor receptor are common in microsatellite instability-high endometrial and colorectal carcinomas.Archives of pathology & laboratory medicine · 2012Article
- Villin expression is frequently lost in poorly differentiated colon cancer.The American journal of pathology · 2012Article
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Colorectal cancers (CRC) with microsatellite instability (MSI) have clinical, pathologic, genetic, and epigenetic features distinct from microsatellite-stable CRC. Examination of epidermal growth factor receptor (EGFR) mRNA and protein expression levels in a panel of colon cancer cell lines identified strong expression of EGFR in multiple cell lines with MSI. Although no relationship between EGFR overexpression and the length of a CA dinucleotide repeat in intron 1 was observed, a variant A13/A14 repeat sequence within the 3'-untranslated region (3'-UTR) of the EGFR gene was identified, which was mutated by either mononucleotide or dinucleotide adenosine deletions in 64% of MSI cell lines and 69% of MSI colon tumors. Using a Tet-Off system, we show that this mutation increases EGFR mRNA stability in colon cancer cells, providing a mechanistic basis for EGFR overexpression in MSI colon cancer cell lines. To determine whether this mutation is a driver or a bystander event in MSI colon cancer, we examined the effect of pharmacologic and molecular inhibition of EGFR in EGFR 3'-UTR mutant MSI cell lines. Cell lines with an EGFR 3'-UTR mutation and that were wild-type (WT) for downstream signaling mediators in the Ras/BRAF and PIK3CA/PTEN pathways were sensitive to EGFR inhibition, whereas those harboring mutations in these signaling mediators were not. Furthermore, in cell lines WT for downstream signaling mediators, those with EGFR 3'-UTR mutations were more sensitive to EGFR inhibition than EGFR 3'-UTR WT cells, suggesting that this mutation provides a growth advantage to this subset of MSI colon tumors.
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