Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Medical Oncology
Published in: Medical Oncology 3/2010

01-09-2010 | Original Paper

High-resolution melting analysis of ADAMTS18 methylation levels in gastric, colorectal and pancreatic cancers

Authors: Zhi Li, Wei Zhang, Yong Shao, Chao Zhang, Qi Wu, Hong Yang, Xiangbin Wan, Jie Zhang, Ming Guan, Jun Wan, Bo Yu

Published in: Medical Oncology | Issue 3/2010

Login to get access

Abstract

A disintegrin and metalloprotease with trombospondin motifs (ADAMTS) is a family of proteins characterized by the presence of a metalloproteinase domain linked to a variety of specialized ancillary domains. ADAMTS18 is a putative tumor suppressive gene related to nasopharyngeal carcinoma. We used high-resolution melting (HRM) analysis to detect the methylation levels of ADAMTS18 gene in 100 gastric cancers, 100 colorectal cancers, 70 pancreatic cancers, and equal number of adjacent normal tissues. The frequency of ADAMTS18 methylation in all three types of cancers was significantly higher than that in normal tissues. Expression levels of ADAMTS18 were inversely correlated with methylation levels. No significant association was found between ADAMTS18 methylation status and TNM staging in the cancers. In summary, epigenetic regulation of ADAMTS18 was associated with carcinogenesis. The application of HRM analysis is a fast and high-throughput way to investigate the epigenetic status of ADAMTS18.
Appendix
Available only for authorised users
Literature
1.
Apte SS. A disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motifs: the ADAMTS family. Int J Biochem Cell Biol. 2004;36(6):981–5.CrossRefPubMed
2.
Lopez-Otin C, Matrisian LM. Emerging roles of proteases in tumour suppression. Nat Rev Cancer. 2007;7(10):800–8.CrossRefPubMed
3.
Porter S, Clark IM, Kevorkian L, Edwards DR. The ADAMTS metalloproteinases. Biochem J. 2005;386(Pt 1):15–27.PubMed
4.
Rocks N, et al. Emerging roles of ADAM and ADAMTS metalloproteinases in cancer. Biochimie. 2008;90(2):369–79.CrossRefPubMed
5.
Tang BL. ADAMTS: a novel family of extracellular matrix proteases. Int J Biochem Cell Biol. 2001;33(1):33–44.CrossRefPubMed
6.
Tortorella MD, et al. Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins. Science. 1999;284(5420):1664–6.CrossRefPubMed
7.
Tortorella MD, Liu RQ, Burn T, Newton RC, Arner E. Characterization of human aggrecanase 2 (ADAM-TS5): substrate specificity studies and comparison with aggrecanase 1 (ADAM-TS4). Matrix Biol. 2002;21(6):499–511.CrossRefPubMed
8.
Kuno K, et al. ADAMTS-1 cleaves a cartilage proteoglycan, aggrecan. FEBS Lett. 2000;478(3):241–5.CrossRefPubMed
9.
Demircan K, et al. ADAMTS-9 is synergistically induced by interleukin-1beta and tumor necrosis factor alpha in OUMS-27 chondrosarcoma cells and in human chondrocytes. Arthritis Rheum. 2005;52(5):1451–60.CrossRefPubMed
10.
Dunn JR, et al. Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is downregulated in brain tumours. Br J Cancer. 2006;94(8):1186–93.CrossRefPubMed
11.
Vazquez F, et al. METH-1, a human ortholog of ADAMTS-1, and METH-2 are members of a new family of proteins with angio-inhibitory activity. J Biol Chem. 1999;274(33):23349–57.CrossRefPubMed
12.
Llamazares M, et al. The ADAMTS12 metalloproteinase exhibits anti-tumorigenic properties through modulation of the Ras-dependent ERK signalling pathway. J Cell Sci. 2007;120(Pt 20):3544–52.CrossRefPubMed
13.
Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 2007;8(4):286–98.CrossRefPubMed
14.
Lind GE, et al. ADAMTS1, CRABP1, and NR3C1 identified as epigenetically deregulated genes in colorectal tumorigenesis. Cell Oncol. 2006;28(5–6):259–72.PubMed
15.
Lo PH, et al. Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9. Oncogene. 2007;26(1):148–57.CrossRefPubMed
16.
Lung HL, et al. Characterization of a novel epigenetically-silenced, growth-suppressive gene, ADAMTS9, and its association with lymph node metastases in nasopharyngeal carcinoma. Int J Cancer. 2008;123(2):401–8.CrossRefPubMed
17.
Viloria CG, et al. Genetic inactivation of ADAMTS15 metalloprotease in human colorectal cancer. Cancer Res. 2009;69(11):4926–34.CrossRefPubMed
18.
Jin H, et al. Epigenetic identification of ADAMTS18 as a novel 16q23.1 tumor suppressor frequently silenced in esophageal, nasopharyngeal and multiple other carcinomas. Oncogene. 2007;26(53):7490–8.CrossRefPubMed
19.
Wojdacz TK, Dobrovic A, Hansen LL. Methylation-sensitive high-resolution melting. Nat Protoc. 2008;3(12):1903–8.CrossRefPubMed
20.
Virmani AK, et al. Hierarchical clustering of lung cancer cell lines using DNA methylation markers. Cancer Epidemiol Biomarkers Prev. 2002;11(3):291–7.PubMed
21.
Wittwer CT, Reed GH, Gundry CN, Vandersteen JG, Pryor RJ. High-resolution genotyping by amplicon melting analysis using LCGreen. Clin Chem. 2003;49(6 Pt 1):853–60.CrossRefPubMed
22.
Paz MF, et al. A systematic profile of DNA methylation in human cancer cell lines. Cancer Res. 2003;63(5):1114–21.PubMed
23.
Cameron EE, Baylin SB, Herman JG. p15(INK4B) CpG island methylation in primary acute leukemia is heterogeneous and suggests density as a critical factor for transcriptional silencing. Blood. 1999;94(7):2445–51.PubMed
24.
Hsieh CL. Dependence of transcriptional repression on CpG methylation density. Mol Cell Biol. 1994;14(8):5487–94.PubMed
25.
Taback B, et al. Epigenetic analysis of body fluids and tumor tissues: application of a comprehensive molecular assessment for early-stage breast cancer patients. Ann N Y Acad Sci. 2006;1075:211–21.CrossRefPubMed
26.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed
27.
Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101–8.CrossRefPubMed
28.
Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 1996;93(18):9821–6.CrossRefPubMed
29.
Clark SJ, Harrison J, Paul CL, Frommer M. High sensitivity mapping of methylated cytosines. Nucleic Acids Res. 1994;22(15):2990–7.CrossRefPubMed
30.
Frommer M, et al. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci USA. 1992;89(5):1827–31.CrossRefPubMed
31.
Colella S, Shen L, Baggerly KA, Issa JP, Krahe R. Sensitive and quantitative universal Pyrosequencing methylation analysis of CpG sites. Biotechniques. 2003;35(1):146–50.PubMed
32.
Warnecke PM, et al. Detection and measurement of PCR bias in quantitative methylation analysis of bisulphite-treated DNA. Nucleic Acids Res. 1997;25(21):4422–6.CrossRefPubMed
33.
Wojdacz TK, Hansen LL. Reversal of PCR bias for improved sensitivity of the DNA methylation melting curve assay. Biotechniques 2006;41(3):274, 276, 278.
34.
Kwabi-Addo B, et al. Age-related DNA methylation changes in normal human prostate tissues. Clin Cancer Res. 2007;13(13):3796–802.CrossRefPubMed
Metadata
Title
High-resolution melting analysis of ADAMTS18 methylation levels in gastric, colorectal and pancreatic cancers
Authors
Zhi Li
Wei Zhang
Yong Shao
Chao Zhang
Qi Wu
Hong Yang
Xiangbin Wan
Jie Zhang
Ming Guan
Jun Wan
Bo Yu
Publication date
01-09-2010
Publisher
Springer US
Published in
Medical Oncology / Issue 3/2010
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-009-9323-8

Other articles of this Issue 3/2010

Medical Oncology 3/2010 Go to the issue

Original Paper

Palliative radiotherapy for the skin metastasis of ovarian cancer: a case report and review of the literature

Original Paper

Tumor burden status evaluated by computed tomography scan is of prognostic importance in patients with chronic lymphocytic leukemia

Original Paper

Interstitial lung disease in patients with small cell lung cancer

Original Paper

Aberrant methylation profile of 14-3-3 sigma and its reduced transcription/expression levels in Chinese sporadic female breast carcinogenesis

Original Paper

Inhibition of Notch3 enhances sensitivity to gemcitabine in pancreatic cancer through an inactivation of PI3K/Akt-dependent pathway

Original paper

Radiological assessment following thermoradiation therapy for primary pleural synovial sarcoma: case report

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits