Genome-wide DNA methylation patterns in pancreatic ductal adenocarcinoma reveal epigenetic deregulation of SLIT-ROBO, ITGA2 and MET signaling

International Journal of Cancer. Journal International Du Cancer
Katia NonesSean M Grimmond

Abstract

The importance of epigenetic modifications such as DNA methylation in tumorigenesis is increasingly being appreciated. To define the genome-wide pattern of DNA methylation in pancreatic ductal adenocarcinomas (PDAC), we captured the methylation profiles of 167 untreated resected PDACs and compared them to a panel of 29 adjacent nontransformed pancreata using high-density arrays. A total of 11,634 CpG sites associated with 3,522 genes were significantly differentially methylated (DM) in PDAC and were capable of segregating PDAC from non-malignant pancreas, regardless of tumor cellularity. As expected, PDAC hypermethylation was most prevalent in the 5' region of genes (including the proximal promoter, 5'UTR and CpG islands). Approximately 33% DM genes showed significant inverse correlation with mRNA expression levels. Pathway analysis revealed an enrichment of aberrantly methylated genes involved in key molecular mechanisms important to PDAC: TGF-β, WNT, integrin signaling, cell adhesion, stellate cell activation and axon guidance. Given the recent discovery that SLIT-ROBO mutations play a clinically important role in PDAC, the role of epigenetic perturbation of axon guidance was pursued in more detail. Bisulfite amplicon deep se...Continue Reading

References

Jul 11, 1998·Molecular Biology of the Cell·L S PriceG M Bokoch
Jun 4, 2002·Nature Reviews. Genetics·Peter A Jones, Stephen B Baylin
Nov 9, 2002·Bioinformatics·Long-Cheng Li, Rajvir Dahiya
Apr 3, 2003·Nature Reviews. Cancer·Peter W Laird
Oct 8, 2004·Molecular Cancer·Robert Jaster
Feb 24, 2006·Nature Reviews. Cancer·Stephen B Baylin, Joyce E Ohm
Oct 31, 2006·Nature Genetics·Florian EckhardtStephan Beck
May 10, 2008·Bioinformatics·Pan DuSimon M Lin
Jul 10, 2008·The Journal of Biological Chemistry·Anil PrasadRamesh K Ganju
Nov 14, 2008·Molecular Biology of the Cell·Maria Cristina StellaPaolo M Comoglio
Jun 6, 2009·Molecular Oncology·Aik Choon TanManuel Hidalgo
Aug 27, 2009·Bioinformatics·Kim-Anh Lê CaoSébastien Déjean
Jul 9, 2010·CA: a Cancer Journal for Clinicians·Ahmedin JemalElizabeth Ward
Jul 9, 2010·Nature·Alika K MaunakeaJoseph F Costello
Oct 23, 2010·Gut·Albrecht NeesseDavid A Tuveson
Nov 18, 2010·Biochemical and Biophysical Research Communications·Kazuhiro KikutaTooru Shimosegawa
Jan 27, 2011·PloS One·Fabienne BrenetJoseph M Scandura
Feb 18, 2011·Nature Reviews. Cancer·Patrick MehlenAlain Chédotal
Mar 10, 2011·Nature Medicine·Manuel Rodríguez-Paredes, Manel Esteller
May 26, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Audrey VincentMichael Goggins
Jun 11, 2011·Genome Research·Toshinori HinouePeter W Laird
Jun 28, 2011·Nature Genetics·Kasper Daniel HansenAndrew P Feinberg
Aug 6, 2011·Journal of Mammary Gland Biology and Neoplasia·Gwyndolen C Harburg, Lindsay Hinck
Aug 19, 2011·The Journal of Investigative Dermatology·María R GirottiAndrea S Llera
Sep 3, 2011·Current Genomics·Yannick DelpuPierre Cordelier
Oct 20, 2011·Nature Reviews. Gastroenterology & Hepatology·Victoria Valinluck Lao, William M Grady
May 9, 2012·Nature Reviews. Clinical Oncology·Solange Peters, Alex A Adjei
Jun 20, 2012·Nature Reviews. Gastroenterology & Hepatology·Mert ErkanHelmut Friess
Sep 14, 2012·Frontiers in Physiology·Minoti V ApteJeremy S Wilson
Oct 19, 2012·Science Translational Medicine·Hermioni ZouridisPatrick Tan
Oct 30, 2012·Nature·Andrew V BiankinSean M Grimmond

❮ Previous
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Citations

Feb 26, 2016·Carcinogenesis·Jack Zhang, Andy Babic
Jan 15, 2016·British Journal of Cancer·Srinivasa P PothulaMinoti V Apte
Jan 21, 2016·Immunotherapy·Andrew L CovelerE Gabriela Chiorean
Sep 18, 2015·Acta Histochemica Et Cytochemica·Yuri KameokaSohei Kitazawa
Feb 26, 2016·Nature·Peter BaileySean M Grimmond
Dec 24, 2015·Best Practice & Research. Clinical Endocrinology & Metabolism·Evans Quilichini, Cécile Haumaitre
Jun 14, 2015·Cancer Letters·Shilong HanMaoquan Li
Feb 11, 2015·The Prostate·Suyin Paulynn ChinJoanne L Dickinson
May 29, 2015·Nature·Ann-Marie PatchDavid D L Bowtell
May 10, 2016·Nature Reviews. Disease Primers·Jorg KleeffJohn P Neoptolemos
Feb 27, 2015·Nature·Nicola WaddellSean M Grimmond
Jun 9, 2016·Diagnostic Pathology·Wenzel M HackengLodewijk A A Brosens
Dec 22, 2016·International Journal of Molecular Sciences·Brittany R Silverman, Jiaqi Shi
Mar 16, 2017·Nutrients·Andee Weisbeck, Rick J Jansen
Mar 17, 2017·Scandinavian Journal of Gastroenterology·Pascal SyrenDaniel Ansari
Jan 11, 2019·Journal of Toxicology and Environmental Health. Part a·Jin WangJian-Xiang Li
Jan 15, 2019·Current Pharmaceutical Design·Sadaf Ghanaatgar-KasbiGordon A Ferns
May 10, 2019·JCO Clinical Cancer Informatics·Vandana SandhuBenjamin Haibe-Kains
Sep 16, 2017·Advances in Anatomic Pathology·Matthäus FelsensteinLaura D Wood
Apr 21, 2017·Oncotarget·Nitish Kumar Mishra, Chittibabu Guda
May 5, 2016·Oncotarget·Noriyuki OmuraMichael Goggins
Aug 19, 2020·Cellular Oncology (Dordrecht)·Cansu TekinC Arnold Spek
Sep 1, 2015·Personalized Medicine·Raphaël MaréchalJean-Luc Van Laethem

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