ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Global promoter methylation analysis reveals novel candidate tumor suppressor genes in natural killer cell lymphoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled 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.
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
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Clinical effect of DAPK promoter methylation in gastric cancer: A systematic meta-analysis.Medicine · 2016Pooled it
- Article
- Identification of methylation-sensitive human transcription factors using meSMiLE-seq.Nature communications · 2026Article
- Tumor metabolic adaptation induced by L-asparaginase reveals a vulnerability to PARP1/2 inhibitor in B-cell lymphomas.Nature communications · 2026Article
- Extranodal NK/T-cell lymphoma: an update of the molecular characterization of the tumor and microenvironment, and its clinical implications.The Lancet regional health. Western Pacific · 2025Review
- The Neglected Suppressor of Cytokine Signalling (SOCS): SOCS4-7.Inflammation · 2025Review
- Distinct epigenetic and transcriptional profiles of Epstein-Barr virus-positive and negative primary CNS lymphomas.Neuro-oncology · 2025Article
- Genetic and Epigenetic Aberrations ofCurrent issues in molecular biology · 2025Article
- Review
- Resistance mechanisms and potential therapeutic strategies in relapsed or refractory natural killer/T cell lymphoma.Chinese medical journal · 2024Review
- MYC overexpression in natural killer cell lymphoma: prognostic and therapeutic implications.Haematologica · 2024Article
- Wemics: A Single-Base Resolution Methylation Quantification Method for Enhanced Prediction of Epigenetic Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Therapeutic challenges in peripheral T-cell lymphoma.Molecular cancer · 2024Review
- Consideration of SHP-1 as a Molecular Target for Tumor Therapy.International journal of molecular sciences · 2023Review
- Biology and genetics of extranodal mature T-cell and NKcell lymphomas and lymphoproliferative disorders.Haematologica · 2023Review
- Novel target and treatment agents for natural killer/T-cell lymphoma.Journal of hematology & oncology · 2023Review
- Super-enhancer-driven TOX2 mediates oncogenesis in Natural Killer/T Cell Lymphoma.Molecular cancer · 2023Article
- Mature T-cell and NK-cell lymphomas: updates on molecular genetic features.International journal of hematology · 2023Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
purposeTo identify tumor suppressor genes epigenetically silenced by promoter hypermethylation in extranodal natural killer cell lymphoma (NKCL). EXPERIMENTAL
designPromoter methylation was analyzed with global and locus-specific methylation assays in NKCL cases and NK cell lines. Gene expression profiles were used to identify genes for which aberrant promoter methylation was associated with transcriptional silencing. Selected DNA methylations were validated by RRBS, pyrosequencing, or q-MSP. Decitabine treatment was performed to evaluate reactivation of methylated genes. The tumor suppressor effect of silenced genes was evaluated functionally by reintroducing them into NK cell lines.
resultsWe observed significant promoter hypermethylation in most NKCL samples compared with normal NK cells. Correlation of global promoter methylation with gene expression profiles identified 95 genes with strong evidence for being silenced because of promoter methylation, including BCL2L11 (BIM), DAPK1, PTPN6 (SHP1), TET2, SOCS6, and ASNS. Known tumor suppressor genes were significantly overrepresented in this set of genes. Decitabine treatment of NK cell lines was associated with reexpression of all 10 selected methylated and silenced genes. Ectopic expression of frequently silenced BIM in two BIM-nonexpressing NK cell lines led to increased apoptosis and eventual elimination of BIM-transduced cells. It also sensitized these cell lines to chemotherapy-induced apoptosis. Similarly, reintroduction of SOCS6 significantly inhibited growth in SOCS6-nonexpressing NK cell lines. NK cell lines lacking ASNS expression showed increased sensitivity to treatment with l-asparaginase. Reintroduction of ASNS reduced drug sensitivity.
conclusionPromoter region hypermethylation is frequent in NKCL, and aberrantly methylated genes are pathologically and clinically significant.
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.