Evidence map›Paper›PMID 21551254›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011

Integrated, genome-wide screening for hypomethylated oncogenes in salivary gland adenoid cystic carcinoma.

Chunbo Shao, Wenyue Sun, Marietta Tan, Chad A Glazer, Sheetal Bhan, Xiaoli Zhong, Carole Fakhry, Rajni Sharma, William H Westra, Mohammad O Hoque and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 4% 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

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.

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  16. Ion Channel Dysregulation in Head and Neck Cancers: Perspectives for Clinical Application.Reviews of physiology, biochemistry and pharmacology · 2021
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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

14 authors at 3 institutions in 1 country.

Chunbo ShaoDepartment of Otolaryngology-Head and Neck Surgery and Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Wenyue Sun
Marietta Tan
Chad A Glazer
Sheetal Bhan
Xiaoli Zhong
Carole Fakhry
Rajni Sharma
William H Westra
Mohammad O Hoque
Christopher A Moskaluk
David Sidransky
Joseph A Califano
Patrick K Ha
University of Virginia · USGreater Baltimore Medical Center · USJohns Hopkins University · US

Funding

TUMOR SUPPRESOR GENE PROMOTER HYPERMETHYLATION FOR DETECTION OF HEAD AND NECKP50DE019032 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI WESTRA, WILLIAM H · 2007 to 2016
$27.1M
Molecular characterization of a human salivary gland tumor xenograft bankRC1DE020687 · NIDCR · UNIVERSITY OF VIRGINIA · PI MOSKALUK, CHRISTOPHER A. · 2009 to 2010
$1000k
The role of promoter hypermethylation in adenoid cystic carcinomaK08DE018463 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI HA, PATRICK KYONGMIN · 2007 to 2011
$674k
NIDCR NIH HHS K08 DE018463NIDCR NIH HHS P50 DE019032NIDCR NIH HHS RC1 DE020687
6 · The paper itself

Abstract

purposeSalivary gland adenoid cystic carcinoma (ACC) is a rare malignancy that is poorly understood. To look for relevant oncogene candidates under the control of promoter methylation, an integrated, genome-wide screen was conducted. EXPERIMENTAL

designGlobal demethylation of normal salivary gland cell strains using 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin A (TSA), followed by expression array analysis was conducted. ACC-specific expression profiling was generated using expression microarray analysis of primary ACC and normal samples. Next, the two profiles were integrated to identify a subset of genes for further validation of promoter demethylation in ACC versus normal. Finally, promising candidates were further validated for mRNA, protein, and promoter methylation levels in larger ACC cohorts. Functional validation was then conducted in cancer cell lines.

resultsWe found 159 genes that were significantly re-expressed after 5-aza-dC/TSA treatment and overexpressed in ACC. After initial validation, eight candidates showed hypomethylation in ACC: AQP1, CECR1, C1QR1, CTAG2, P53AIP1, TDRD12, BEX1, and DYNLT3. Aquaporin 1 (AQP1) showed the most significant hypomethylation and was further validated. AQP1 hypomethylation in ACC was confirmed with two independent cohorts. Of note, there was significant overexpression of AQP1 in both mRNA and protein in the paraffin-embedded ACC cohort. Furthermore, AQP1 was upregulated in 5-aza-dC/TSA-treated SACC83. Finally, AQP1 promoted cell proliferation and colony formation in SACC83.

conclusionsOur integrated, genome-wide screening method proved to be an effective strategy for detecting novel oncogenes in ACC. AQP1 is a promising oncogene candidate for ACC and is transcriptionally regulated by promoter hypomethylation.

Indexed as

Genetic TestingGenome-Wide Association StudyAdultAgedAged, 80 and overAntimetabolites, AntineoplasticAquaporin 1AzacitidineCarcinoma, Adenoid CysticCell LineCell Line, TumorCell ProliferationCytidine TriphosphateDNA MethylationEpigenomicsFemale5-aza-2'-deoxycytidine-5'-triphosphateAntimetabolites, AntineoplasticAQP1 protein, humanAquaporin 1AzacitidineCytidine Triphosphate

Identifiers

PMID21551254
PMCPMC3131484
OpenAlexW2116208810

What OpenQuestion holds

Textmetadata
LicenceTDM
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.