Evidence map›Paper›PMID 27212063›Full record

ArticleInternational journal of oncology2016

Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening.

Shizhang Ling, Eleni M Rettig, Marietta Tan, Xiaofei Chang, Zhiming Wang, Mariana Brait, Justin A Bishop, Elana J Fertig, Michael Considine, Michael J Wick and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. Construction of a prediction model for prognosis of bladder cancer based on the expression of ion channel-related genes.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023
    Article
  4. Review
  5. Genomics of mucoepidermoid and adenoid cystic carcinomas.Laryngoscope investigative otolaryngology · 2018
    Review
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

11 authors at 3 institutions in 1 country.

Shizhang LingDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD 21231, USA.
Eleni M RettigDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD 21231, USA.
Marietta TanDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD 21231, USA.
Xiaofei ChangDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD 21231, USA.
Zhiming WangDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD 21231, USA.
Mariana BraitDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD 21231, USA.
Justin A BishopDepartment of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
Elana J FertigDepartment of Oncology Biostatistics, Johns Hopkins University, Baltimore, MD 21231, USA.
Michael ConsidineDepartment of Oncology Biostatistics, Johns Hopkins University, Baltimore, MD 21231, USA.
Michael J WickSouth Texas Accelerated Research Therapeutics (START), Preclinical Research, 4383 Medical Drive, San Antonio, TX 78229, USA.
Patrick K HaDepartment of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA 94158, USA.
Johns Hopkins University · USSouth Texas Accelerated Research Therapeutics · USUniversity of California, San Francisco · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Integrated pathway analysis of altered driver genes in adenoid cystic carcinomaR01DE023227 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HA, PATRICK KYONGMIN · 2012 to 2015
$1.6M
array-based screening for the expression and regulation of tumor supressor genesR03DE022591 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI HA, PATRICK KYONGMIN · 2012 to 2013
$241k
NCI NIH HHS P30 CA006973NIDCR NIH HHS R01 DE023227NIDCR NIH HHS R03 DE022591
6 · The paper itself

Abstract

Salivary gland adenoid cystic carcinoma (ACC) is a rare head and neck malignancy without molecular biomarkers that can be used to predict the chemotherapeutic response or prognosis of ACC. The regulation of gene expression of oncogenes and tumor suppressor genes (TSGs) through DNA promoter methylation may play a role in the carcinogenesis of ACC. To identify differentially methylated genes in ACC, a global demethylating agent, 5-aza-2'-deoxycytidine (5-AZA) was utilized to unmask putative TSG silencing in ACC xenograft models in mice. Fresh xenografts were passaged, implanted in triplicate in mice that were treated with 5-AZA daily for 28 days. These xenografts were then evaluated for genome-wide DNA methylation patterns using the Illumina Infinium HumanMethylation27 BeadChip array. Validation of the 32 candidate genes was performed by bisulfite sequencing (BS-seq) in a separate cohort of 6 ACC primary tumors and 6 normal control salivary gland tissues. Hypermethylation was identified in the HCN2 gene promoter in all 6 control tissues, but hypomethylation was found in all 6 ACC tumor tissues. Quantitative validation of HCN2 promoter methylation level in the region detected by BS-seq was performed in a larger cohort of primary tumors (n=32) confirming significant HCN2 hypomethylation in ACCs compared with normal samples (n=10; p=0.04). HCN2 immunohistochemical staining was performed on an ACC tissue microarray. HCN2 staining intensity and H-score, but not percentage of the positively stained cells, were significantly stronger in normal tissues than those of ACC tissues. With our novel screening and sequencing methods, we identified several gene candidates that were methylated. The most significant of these genes, HCN2, was actually hypomethylated in tumors. However, promoter methylation status does not appear to be a major determinant of HCN2 expression in normal and ACC tissues. HCN2 hypomethylation is a biomarker of ACC and may play an important role in the carcinogenesis of ACC.

Indexed as

AdultAgedAnimalsBiomarkers, TumorCarcinoma, Adenoid CysticCell Line, TumorDNA MethylationFemaleGene Expression Regulation, NeoplasticHumansHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMaleMiceMiddle AgedPrognosisPromoter Regions, GeneticBiomarkers, TumorHyperpolarization-Activated Cyclic Nucleotide-Gated Channels

Identifiers

PMID27212063
PMCPMC4902070
OpenAlexW2408226075

What OpenQuestion holds

Textmetadata
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.