Evidence map›Paper›PMID 26634009›Full record

ArticleClinical epigenetics2015

Epigenetic inactivation of the extracellular matrix metallopeptidase ADAMTS19 gene and the metastatic spread in colorectal cancer.

Sergio Alonso, Beatriz González, Tatiana Ruiz-Larroya, Mercedes Durán Domínguez, Takaharu Kato, Akihiro Matsunaga, Koichi Suzuki, Alex Y Strongin, Pepita Gimènez-Bonafé, Manuel Perucho

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

14 citing papers in PubMed, 28 citations in OpenAlex.

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  14. Epigenetic Biomarkers in Colorectal Cancer.Molecular diagnosis & therapy · 2017
    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

10 authors at 5 institutions in 3 countries.

Sergio AlonsoInstitute of Predictive and Personalized Medicine of Cancer (IMPPC), Institut d'investigació en ciéncies de la salut Germans Trias I Pujol, (IGTP), Campus Can Ruti, 08916 Badalona, Barcelona Spain.
Beatriz GonzálezInstitute of Predictive and Personalized Medicine of Cancer (IMPPC), Institut d'investigació en ciéncies de la salut Germans Trias I Pujol, (IGTP), Campus Can Ruti, 08916 Badalona, Barcelona Spain.
Tatiana Ruiz-LarroyaInstitute of Predictive and Personalized Medicine of Cancer (IMPPC), Institut d'investigació en ciéncies de la salut Germans Trias I Pujol, (IGTP), Campus Can Ruti, 08916 Badalona, Barcelona Spain ; Sanford Burnham Prebys Medical Dicovery Institute, 10901 N. Torrey Pines Rd. La Jolla, San Diego, CA 92037 USA.
Mercedes Durán DomínguezCancer Genetics Laboratory, IBGM-CSIC, University of Valladolid, Valladolid, 47005 Spain.
Takaharu KatoInstitute of Predictive and Personalized Medicine of Cancer (IMPPC), Institut d'investigació en ciéncies de la salut Germans Trias I Pujol, (IGTP), Campus Can Ruti, 08916 Badalona, Barcelona Spain ; Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503 Japan.
Akihiro MatsunagaSanford Burnham Prebys Medical Dicovery Institute, 10901 N. Torrey Pines Rd. La Jolla, San Diego, CA 92037 USA.
Koichi SuzukiDepartment of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503 Japan.
Alex Y StronginSanford Burnham Prebys Medical Dicovery Institute, 10901 N. Torrey Pines Rd. La Jolla, San Diego, CA 92037 USA.
Pepita Gimènez-BonaféInstitute of Predictive and Personalized Medicine of Cancer (IMPPC), Institut d'investigació en ciéncies de la salut Germans Trias I Pujol, (IGTP), Campus Can Ruti, 08916 Badalona, Barcelona Spain ; Departament de Ciències Fisiològiques II, Campus Ciènces de Salut de Bellvitge, IDIBELL, University of Barcelona, Barcelona, 08907 Spain.
Manuel PeruchoInstitute of Predictive and Personalized Medicine of Cancer (IMPPC), Institut d'investigació en ciéncies de la salut Germans Trias I Pujol, (IGTP), Campus Can Ruti, 08916 Badalona, Barcelona Spain ; Sanford Burnham Prebys Medical Dicovery Institute, 10901 N. Torrey Pines Rd. La Jolla, San Diego, CA 92037 USA ; Institució Catalana de Recerca i Estudis Avançats (ICREA), Catalan Institution for Research and Advanced Studies. Pg. Lluís Companys 23, 08010 Barcelona, Spain.
Institute of Predictive and Personalized Medicine of Cancer · ESSanford Burnham Prebys Medical Discovery Institute · USInstitut d'Investigació Biomédica de Bellvitge · ESInstituto de Biomedicina y Genética Molecular de Valladolid · ESJichi Medical University · JP

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
MOLECULAR PATHOGENESIS OF CANCER OF MUTATOR PHENOTYPER37CA063585 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI PERUCHO, MANUEL · 1999 to 2008
$7.0M
NCI NIH HHS P30 CA030199NCI NIH HHS R37 CA063585
6 · The paper itself

Abstract

backgroundADAMTS19 encodes a member of the ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) protein family with emerging roles in carcinogenesis and metastasis. ADAMTS shares several distinct protein modules including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. In a previous work, we found ADAMTS19 frequently hypermethylated in colorectal cancer (CRC). We explored the association of methylation with tumor genotype and phenotype.

resultsThe methylation status of the CpG island in the promoter of ADAMTS19 was determined in 252 colorectal, 65 pancreatic, 33 breast and 169 ovarian primary tumors, 70 CRC metastases, and 10 CRC cell lines. Tumor-specific methylation of ADAMTS19 was significantly more frequent in gastrointestinal than in gynecological cancers (odds ratio (OR) = 2.9, confidence interval (CI) = (1.9-4.7), p = 5.2 × 10(-7)) and was independent of the methylation of adjacent loci in CRC. Hypermethylation associated with CRC with mutated BRAF oncogene (OR = 10.1, CI = (3.1-42.9), p = 6.3 × 10(-6)) and with the mucinous phenotype in CRC (OR = 2.1, CI = (1.1-4.1), p = 0.023) and ovarian cancer (OR = 60, CI = (16-346), p = 4 × 10(-16)). Methylation was significantly more frequent in CRC metastases homing to the ovary and omentum than in those homing to the liver and lung (OR = 6.1, CI = (1.8-22.2), p = 0.001). Differentiating local from distant metastatic spread, methylation negatively associated with tumor progression (p = 0.031) but positively with depth of invasion (p = 0.030). Hypermethylation associated with transcriptional repression in CRC cell lines, and treatment with 5'-AZA-2'-deoxycytidine led to reactivation of mRNA expression. shRNA-mediated silencing of ADAMTS19 had no effect on the in vitro proliferation rate of CRC cells but significantly diminished their collective migration speed (56 %, p = 3.3 × 10(-4)) and potential to migrate in collagen I (64 %, p = 4.3 × 10(-10)).

conclusionsOur results highlight the frequent involvement of ADAMTS19 epigenetic silencing in CRC and mucinous ovarian cancer. The mechanistic preferences for the target organ of metastatic spread may lead to the development of diagnostic CRC biomarkers. The association with the mucinous phenotype also may have diagnostic applications for ovarian cancer.

Indexed as

ADAMTSGastrointestinal cancerMatrix metallopeptidasesMethylationMS-AFLPOvarian cancer

Identifiers

PMID26634009
PMCPMC4667455
OpenAlexW2181696126

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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.