ArticleNature2015
Alternative transcription initiation leads to expression of a novel ALK isoform in cancer.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 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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Who cites it
133 citing papers in PubMed, 248 citations in OpenAlex.
- Endogenous retrovirus control of calbindin is essential for human early embryogenesis.Science advances · 2026Article
- ALK ATI in solid tumours: biological evidence, diagnostic challenges, and clinical relevance. a narrative review.Molecular biology reports · 2026Review
- Three decades of anaplastic lymphoma kinase: from physiological roles to cancer and immune evasion.Cancer metastasis reviews · 2026Review
- Unannotated noncoding transcripts as a source of intratumor heterogeneity in malignant cell states.Science China. Life sciences · 2026Article
- Out-of-frame CBX3::ALK fusion drives ALK activation and therapy response.Cell reports. Medicine · 2026Article
- Systematic transcriptome analysis reveals the function of alternative promoters in hematopoietic lineages.Stem cell reports · 2026Article
- ALK-positive histiocytosis and a clonally related chronic myelomonocytic leukemia.Haematologica · 2026Article
- Endogenous retroviruses in aging and cancer: from genomic defense to oncogenic activation.Mobile DNA · 2025Review
- The expression, regulation, and function of human endogenous retroviruses in genitourinary cancers.Cell death discovery · 2025Review
- Transcriptional and post-transcriptional regulation of transposable elements and their roles in development and disease.Nature reviews. Molecular cell biology · 2025Review
- Review
- Lung Adenocarcinoma Expressing an EML4-ALK Fusion Transcript With Premature Stop Codons and Response to Alectinib: A Case Report.Thoracic cancer · 2025Article
- Spatial organization of chromatin restricts activation of poised alternative promoters in LTRs.Nature genetics · 2025Article
- Disruption of TAD hierarchy promotes LTR co-option in cancer.Nature genetics · 2025Article
- Retroelement co-option disrupts the cancer transcriptional programme.Genome medicine · 2025Article
- ALK in cancer: from function to therapeutic targeting.Nature reviews. Cancer · 2025Review
- Predicting and comparing transcription start sites in single cell populations.PLoS computational biology · 2025Article
- Discovery of Gene Fusions in Driver-Negative Cancer Samples From the National Cancer Institute-Molecular Analysis for Therapy Choice Screening Cohort.JCO precision oncology · 2024Article
- A New Approach of DetectingCancers · 2024Article
- Correlations of Long Noncoding RNA HNF4A-AS1 Alternative Transcripts with Liver Diseases and Drug Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
73 more citing papers are in PubMed but not listed here.
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Authors and funding
32 authors at 5 institutions in 2 countries.
Funding
Abstract
Activation of oncogenes by mechanisms other than genetic aberrations such as mutations, translocations, or amplifications is largely undefined. Here we report a novel isoform of the anaplastic lymphoma kinase (ALK) that is expressed in ∼11% of melanomas and sporadically in other human cancer types, but not in normal tissues. The novel ALK transcript initiates from a de novo alternative transcription initiation (ATI) site in ALK intron 19, and was termed ALK(ATI). In ALK(ATI)-expressing tumours, the ATI site is enriched for H3K4me3 and RNA polymerase II, chromatin marks characteristic of active transcription initiation sites. ALK(ATI) is expressed from both ALK alleles, and no recurrent genetic aberrations are found at the ALK locus, indicating that the transcriptional activation is independent of genetic aberrations at the ALK locus. The ALK(ATI) transcript encodes three proteins with molecular weights of 61.1, 60.8 and 58.7 kilodaltons, consisting primarily of the intracellular tyrosine kinase domain. ALK(ATI) stimulates multiple oncogenic signalling pathways, drives growth-factor-independent cell proliferation in vitro, and promotes tumorigenesis in vivo in mouse models. ALK inhibitors can suppress the kinase activity of ALK(ATI), suggesting that patients with ALK(ATI)-expressing tumours may benefit from ALK inhibitors. Our findings suggest a novel mechanism of oncogene activation in cancer through de novo alternative transcription initiation.
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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.