Epigenetic Alterations in Pancreatic Cancer

Ayars, Michael; Goggins, Michael

doi:10.1007/978-1-4614-6549-2_9

Cited by 2 publications

(2 citation statements)

References 133 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pancreatic ductal adenocarcinomas develop as a result of clonally-selected genetic events most commonly involving the genes KRAS, CDKN2A, TP53 and SMAD4 [2-6], less commonly ATM and others [3, 5, 7, 8], and for pancreatic ductal adenocarcinomas arising from intraductal papillary mucinous neoplasms, most commonly KRAS, CDKN2A, TP53 , as well as GNAS and RNF43 [9-11]. Previous studies have demonstrated that aberrant expression of epigenetically regulated genes contributes to pancreatic cancer development and progression [12-16]. To further identify epigenetically deregulated genes in pancreatic cancers, we compared the published SAGE (Serial analysis of gene expression) profiles of pancreatic ductal adenocarcinomas and normal pancreatic duct cells [3], focusing on silenced genes implicated in cancer progression that had not been reported as silenced in pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic silencing of EYA2 in pancreatic adenocarcinomas promotes tumor growth

Vincent

Hong

et al. 2014

Oncotarget

Self Cite

View full text Add to dashboard Cite

To identify potentially important genes dysregulated in pancreatic cancer, we analyzed genome-wide transcriptional analysis of pancreatic cancers and normal pancreatic duct samples and identified the transcriptional coactivator, EYA2 (Drosophila Eyes Absent Homologue-2) as silenced in the majority of pancreatic cancers. We investigated the role of epigenetic mechanisms of EYA2 gene silencing in pancreatic cancers, performed in vitro and in vivo proliferation and migration assays to assess the effect of EYA2 silencing on tumor cell growth and metastasis formation, and expression analysis to identify genes transcriptionally regulated by EYA2. We found loss of tumoral Eya2 expression in 63% of pancreatic cancers (120/189 cases). Silencing of EYA2 expression in pancreatic cancer cell lines correlated with promoter methylation and histone deacetylation and was reversible with DNA methyltransferase and HDAC inhibitors. EYA2 knockdown in pancreatic cancer cell lines increased cell proliferation. Compared to parental pancreatic cancer cells, pancreatic cancers stably-expressing EYA2 grew more slowly and had fewer metastases in orthotopic models. The transcriptional changes after stable expression of EYA2 in pancreatic cancer cells included induction of genes in the TGFbeta pathway. Epigenetic silencing of EYA2 is a common event in pancreatic cancers and stable expression EYA2 limits the growth and metastases of pancreatic adenocarcinoma.

show abstract

Section: Introductionmentioning

confidence: 99%

Epigenetic silencing of EYA2 in pancreatic adenocarcinomas promotes tumor growth

Vincent

Hong

et al. 2014

Oncotarget

Self Cite

View full text Add to dashboard Cite

show abstract

“…Tumoural loss of gene expression arises not only through genetic mechanisms, such as homozygous deletion of genes, but also through epigenetic silencing. 9 The detection of these losses is not possible without isolating pure populations of cells using actual microdissection or other techniques such as FACS analysis. 10 Similarly, potentially important changes in the expression of genes from a tumour cell that might also be expressed by other cells within the tumour microenvironment are not adequately determined in a virtual microdissection analysis.…”

mentioning

confidence: 99%