ArticleGenes, chromosomes & cancer2011
Germline and somatic DNA methylation and epigenetic regulation of KILLIN in renal cell carcinoma.
Article in Genes, chromosomes & cancer, 2011. 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, 37 citations in OpenAlex.
- Epithelial-mesenchymal transition and sunitinib resistance in renal cell carcinoma: mechanisms and therapeutic strategies.Frontiers in pharmacology · 2026Review
- Rare Hereditary Gynecological Cancer Syndromes.International journal of molecular sciences · 2022Review
- circAMOTL1L Suppresses Renal Cell Carcinoma Growth by Modulating the miR-92a-2-5p/KLLN Pathway.Oxidative medicine and cellular longevity · 2021Article
- Identification of nuclear export signal in KLLN suggests potential role in proteasomal degradation in cancer cells.Oncotarget · 2020Article
- KLLN-mediated DNA damage-induced apoptosis is associated with regulation of p53 phosphorylation and acetylation in breast cancer cells.Cell death discovery · 2018Article
- Circulating levels of PTEN and KLLN in papillary thyroid carcinoma: can they be considered as novel diagnostic biomarkers?Endocrine · 2017Article
- The epigenetic landscape of renal cancer.Nature reviews. Nephrology · 2017Review
- Cancer-predisposition gene KLLN maintains pericentric H3K9 trimethylation protecting genomic stability.Nucleic acids research · 2016Article
- Epigenomics of clear cell renal cell carcinoma: mechanisms and potential use in molecular pathology.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2016Review
- XTEN as Biological Alternative to PEGylation Allows Complete Expression of a Protease-Activatable Killin-Based Cytostatic.PloS one · 2016Article
- KLLN epigenotype-phenotype associations in Cowden syndrome.European journal of human genetics : EJHG · 2015Article
- Role of DNA methylation in renal cell carcinoma.Journal of hematology & oncology · 2015Review
- The epigenetic landscape of clear-cell renal cell carcinoma.Journal of kidney cancer and VHL · 2015Article
- Cell cycle specific distribution of killin: evidence for negative regulation of both DNA and RNA synthesis.Cell cycle (Georgetown, Tex.) · 2015Article
- Germline and somatic KLLN alterations in breast cancer dysregulate G2 arrest.Human molecular genetics · 2013Article
- A reinvestigation of somatic hypermethylation at the PTEN CpG island in cancer cell lines.Biological procedures online · 2012Article
- Genome-wide screening of genes regulated by DNA methylation in colon cancer development.PloS one · 2012Article
- microRNA-21 governs TORC1 activation in renal cancer cell proliferation and invasion.PloS one · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
We recently identified germline methylation of KILLIN, a novel p53-regulated tumor suppressor proximal to PTEN, in >1/3 Cowden or Cowden syndrome-like (CS/CSL) individuals who are PTEN mutation negative. Individuals with germline KILLIN methylation had increased risks of renal cell carcinoma (RCC) over those with PTEN mutations. Therefore, we tested the hypothesis that KILLIN may be a RCC susceptibility gene, silenced by germline methylation. We found germline hypermethylation by combined bisulfite restriction analysis in at least one of the four CpG-rich regions in 23/41 (56%) RCC patients compared to 0/50 controls (P < 0.0001). Of the 23, 11 (48%) demonstrated methylation in the -598 to -890 bp region in respect to the KILLIN transcription start site. Furthermore, 19 of 20 advanced RCC showed somatic hypermethylation upstream of KILLIN, with the majority hypermethylated at more than one CpG island (13/19 vs. 3/23 with germline methylation, P < 0.0001). qRT-PCR revealed that methylation significantly downregulates KILLIN expression (P = 0.05), and demethylation treatment by 5-aza-2'deoxycytidine significantly increased KILLIN expression in all RCC cell lines while only increasing PTEN expression in one line. Furthermore, targeted in vitro methylation revealed a significant decrease in KILLIN promoter activity only. These data reveal differential epigenetic regulation by DNA promoter methylation of this bidirectional promoter. In summary, we have identified KILLIN as a potential novel cancer predisposition gene for nonsyndromic clear-cell RCC, and the epigenetic mechanism of KILLIN inactivation in both the germline and somatic setting suggests the potential for treatment with demethylating agents.
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.