Evidence map›Paper›PMID 17476321›Full record

ArticlePloS one2007

LINE-1 hypomethylation in cancer is highly variable and inversely correlated with microsatellite instability.

Marcos R H Estécio, Vazganush Gharibyan, Lanlan Shen, Ashraf E K Ibrahim, Ketan Doshi, Rong He, Jaroslav Jelinek, Allen S Yang, Pearlly S Yan, Tim H-M Huang and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
142citing papers in PubMed, 2 pooled it
8.8field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

142 citing papers in PubMed, 2 syntheses or guidelines pooled it, 265 citations in OpenAlex.

  1. Pooled it
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  5. Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2009
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  20. Targeting the methionine addiction of cancer.American journal of cancer research · 2022
    Review

82 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Marcos R H EstécioDepartment of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
Vazganush Gharibyan
Lanlan Shen
Ashraf E K Ibrahim
Ketan Doshi
Rong He
Jaroslav Jelinek
Allen S Yang
Pearlly S Yan
Tim H-M Huang
Eloiza H Tajara
Jean-Pierre J Issa
The University of Texas MD Anderson Cancer Center · USCancer Genetics (United States) · USFaculdade de Medicina de São José do Rio Preto · BRSouthern California University for Professional Studies · USUniversity of Cambridge · GBUniversity of Minnesota · US

Funding

University of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KONOPLEVA, MARINA Y · 2003 to 2023
$43.7M
DNA Methylation in Colon Cancer MetastasisR01CA098006 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ISSA, JEAN-PIERRE J. · 2004 to 2008
$1.4M
Diet and DNA methylation in colon mucosa and adenomasR01CA105346 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ISSA, JEAN-PIERRE J · 2004 to 2007
$1.1M
NCI NIH HHS CA098006NCI NIH HHS CA100632NCI NIH HHS CA105346NCI NIH HHS P50 CA100632NCI NIH HHS R01 CA098006NCI NIH HHS R01 CA105346
6 · The paper itself

Abstract

backgroundAlterations in DNA methylation in cancer include global hypomethylation and gene-specific hypermethylation. It is not clear whether these two epigenetic errors are mechanistically linked or occur independently. This study was performed to determine the relationship between DNA hypomethylation, hypermethylation and microsatellite instability in cancer. METHODOLOGY/PRINCIPAL

findingsWe examined 61 cancer cell lines and 60 colorectal carcinomas and their adjacent tissues using LINE-1 bisulfite-PCR as a surrogate for global demethylation. Colorectal carcinomas with sporadic microsatellite instability (MSI), most of which are due to a CpG island methylation phenotype (CIMP) and associated MLH1 promoter methylation, showed in average no difference in LINE-1 methylation between normal adjacent and cancer tissues. Interestingly, some tumor samples in this group showed increase in LINE-1 methylation. In contrast, MSI-showed a significant decrease in LINE-1 methylation between normal adjacent and cancer tissues (P<0.001). Microarray analysis of repetitive element methylation confirmed this observation and showed a high degree of variability in hypomethylation between samples. Additionally, unsupervised hierarchical clustering identified a group of highly hypomethylated tumors, composed mostly of tumors without microsatellite instability. We extended LINE-1 analysis to cancer cell lines from different tissues and found that 50/61 were hypomethylated compared to peripheral blood lymphocytes and normal colon mucosa. Interestingly, these cancer cell lines also exhibited a large variation in demethylation, which was tissue-specific and thus unlikely to be resultant from a stochastic process. CONCLUSION/SIGNIFICANCE: Global hypomethylation is partially reversed in cancers with microsatellite instability and also shows high variability in cancer, which may reflect alternative progression pathways in cancer.

Indexed as

DNA MethylationLong Interspersed Nucleotide ElementsBase SequenceDNA PrimersHumansMicrosatellite RepeatsNeoplasmsDNA Primers

Identifiers

PMID17476321
PMCPMC1851990
OpenAlexW2011831296

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.