Evidence map›Paper›PMID 30509319›Full record

ArticleClinical epigenetics2018

Comprehensive methylation analysis of imprinting-associated differentially methylated regions in colorectal cancer.

Hidenori Hidaka, Ken Higashimoto, Saori Aoki, Hiroyuki Mishima, Chisa Hayashida, Toshiyuki Maeda, Yasuo Koga, Hitomi Yatsuki, Keiichiro Joh, Hirokazu Noshiro and 5 more

Abstract read
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Article in Clinical epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
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

16 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Epigenetic reprogramming in cancer: From diagnosis to treatment.Frontiers in cell and developmental biology · 2023
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. DNA methylation analysis of multiple imprinted DMRs in Sotos syndrome reveals IGF2-DMR0 as a DNA methylation-dependent, P0 promoter-specific enhancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  15. Review
  16. Article
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

15 authors.

Hidenori HidakaDivision of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
Ken HigashimotoDivision of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan. higashim@cc.saga-u.ac.jp.
Saori AokiDivision of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
Hiroyuki MishimaDepartment of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Chisa HayashidaDepartment of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Toshiyuki MaedaDepartment of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan.
Yasuo KogaDepartment of Surgery, Faculty of Medicine, Saga University, Saga, Japan.
Hitomi YatsukiDivision of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
Keiichiro JohDivision of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
Hirokazu NoshiroDepartment of Surgery, Faculty of Medicine, Saga University, Saga, Japan.
Ryuichi IwakiriDepartment of Internal Medicine and Gastrointestinal Endoscopy, Faculty of Medicine, Saga University, Saga, Japan.
Atsushi KawaguchiSection of Clinical Cooperation System, Center for Comprehensive Community Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Koh-Ichiro YoshiuraDepartment of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Kazuma FujimotoDepartment of Internal Medicine and Gastrointestinal Endoscopy, Faculty of Medicine, Saga University, Saga, Japan.
Hidenobu SoejimaDivision of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan. soejimah@cc.saga-u.ac.jp.ORCID 0000-0001-5076-6563

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImprinted genes are regulated by DNA methylation at imprinting-associated differentially methylated regions (iDMRs). Abnormal expression of imprinted genes is implicated in imprinting disorders and tumors. In colorectal cancer (CRC), methylation and imprinting status of the IGF2/H19 domain have been studied. However, no comprehensive methylation analysis of iDMRs in CRC has been reported. Furthermore, the relationship between iDMR methylation status and other methylation-related issues, such as CpG island methylator phenotype (CIMP) and long interspersed element-1 (LINE-1) methylation, remains unclear.

resultsWe analyzed the methylation status of 38 iDMRs in 106 CRC patients. We also investigated CIMP, LINE-1 methylation, KRAS and BRAF gene mutations, and loss of imprinting (LOI) of IGF2. We further examined the relationship between these factors and clinicopathological factors. The overall trend in iDMR methylation was towards hypermethylation, and iDMRs could be grouped into three categories: susceptible, resistant, and intermediate-to-aberrant methylation. The susceptible and resistant iDMRs consisted of all types of iDMR (gametic and somatic, maternally and paternally methylated). Hypermethylation of multiple iDMRs (HyMiD)-positive status was statistically associated with CIMP-positive status, but not associated with mutations in the BRAF and KRAS genes. HyMiD-positive status was inversely associated with LINE-1 methylation. Among four iDMRs within the IGF2/H19 domain, IGF2-DMR0 hypomethylation occurred most frequently, but was not associated with IGF2 LOI. Finally, we statistically calculated predictive prognostic scores based on aberrant methylation status of three iDMRs.

conclusionIn CRC tissues, some iDMRs were susceptible to hypermethylation independent of the type of iDMR and genomic sequence. Although HyMiD-positive status was associated with CIMP-positive status, this was independent of the BRAF and KRAS pathways, which are responsible for CIMP. Since IGF2-DMR0 hypomethylation and aberrant methylation of other iDMRs within the IGF2/H19 domain were not associated with IGF2 LOI, dysfunction of any of the molecular components related to imprinting regulation may be involved in IGF2 LOI. The prognostic score calculated based on aberrant methylation of three iDMRs has potential clinical applications as a prognostic predictor in patients. Further study is required to understand the biological significance of, and mechanisms behind, aberrant methylation of iDMRs and IGF2 LOI in CRCs.

Indexed as

DNA MethylationGenomic ImprintingColorectal NeoplasmsCpG IslandsEpigenomicsFemaleHumansInsulin-Like Growth Factor IILong Interspersed Nucleotide ElementsMalePrognosisProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)RNA, Long NoncodingBRAF protein, humanH19 long non-coding RNAIGF2 protein, humanInsulin-Like Growth Factor IIKRAS protein, humanProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)RNA, Long NoncodingBRAF mutationCIMPDNA methylationGenomic imprintingiDMRIGF2-DMR0IGF2 LOIKRAS mutationLINE-1

Identifiers

PMID30509319
PMCPMC6278095

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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.