Genome-wide DNA methylation profiling of pancreatic neuroendocrine tumors identifies distinct methylation profiles and differentially methylated gene promoter regions associated with low, medium and high grade tumors Abstract #62

Introduction: Integration of genetics and epigenetics has emerged as a powerful approach to studying cellular differentiation (Mikkelsen et al, 2009) and tumorigenesis (Shen et al, 2007). The study of DNA methylation is of particular importance in cancer, as causal involvement has been demonstrated and it is the most stable of all epigenetic modifications, making it a desirable marker for both early detection and treatment of tumors. Hypermethylation of CpG sites in gene promoter regions leads to decreased gene expression; if such a gene is a tumor suppressor, this leads to carcinogenesis. To date, there have been no studies of genome-wide DNA methylation profiling of NETs. This study sets out to determine the DNA methylation profiles of low, intermediate and high grade pancreatic NET liver metastases with the intention of identifying dysregulated biological pathways in the development of these tumors. A protocol for the analysis formalin-fixed paraffin embedded tissue (FFPE) has also been developed in order to study these tumors in significant numbers following this pilot study.
Aim(s): To perform genome-wide DNA methylation anaylsis on 10 fresh frozen pancreatic neuroendocrine tumors of low, intermediate and high grade tumors in order to determine whether these tumors have distinct DNA methylation profiles, and the development of a protocol to analyse formalin-fixed paraffin embedded tissue on the Infinium HumMeth27 array platform in order to study a significant number if tumors.
Materials and methods: Ten fresh frozen sporadic pancreatic NET liver tumors (three low grade, three intermediate grade and four high grade) were analysed using the Illumina HumMeth27 beadarray (which interrogates 27,500 genome-wide CpG sites relating to promoter regions of 14,000 genes and 100 micro-RNAs). DNA was extracted from fresh frozen tumors and 1µg of DNA bisulphite converted following standard protocols before running on the HumMeth27 array. Data analysis: Following inter- and intra-array normalization, features are identified correlating with phenotypes of interest using logistic regression analysis.

To read results and conclusion, please login ...

Further abstracts you may be interested in

#9 Case Management of Metastatic carcinoid of the Foregut,Midgut and Hindgut:the relevance of Ki-67 prognostication
Introduction: The predictive value of tumor grade in the prognosis of carcinoid is insufficient and somehow misleading. The grade and differentiation in carcinoid tumors must be seen in conjunction with the Ki-67 index. The Ki-67 protein is a cellular marker for proliferation, present during all active phases of the cell cycle (G1, S, G2 and mitosis) and absent from resting cells (G0). It is therefore an excellent marker to determine the growth fraction of a given cell population. The Ki-67 labelling index is often correlated with the clinical course of carcinoid.
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: Dr Marianne J Kohler
#11 Plasma chromogranin - A response to octreotide test: Prognostic value for clinical outcome in endocrine digestive tumors
Introduction: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) expressing somatostatin receptors may be treated with somatostatin analogues (SSAs). Selection criteria are a positive Octreoscan® or a >50% hormone level decrease after octreotide s.c. injection (octreotide test) (OT). Plasma chromogranin A (CgA) is the best general GEP-NET marker, but data on CgA response to OT are scant.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: MD, PhD Sara Massironi
#12 Chromogranin A as a predictor of progression, regression or stable disease in ileo-cecal (midgut) carcinoid tumors
Introduction: A general characteristic for NETs is their expression of certain proteins, such as chromogranin A (CgA), which is released from the dense core vesicles of NE cells, occasionally together with cell specific hormones, such as gastrin and serotonin. Plasma CgA seems to be closely related to tumor burden of intestinal carcinoid tumors in humans.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Kenneth Jensen
#13 Neoadjuvant peptide receptor radionuclide therapy for an inoperable neuroendocrine pancreatic carcinoma
Introduction: Pancreatic endocrine tumors (pNETs) are rare but are among the most common neuroendocrine neoplasms of the abdomen. At diagnosis, many of them are already advanced and difficult to treat.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Dr. Daniel Kaemmerer
#14 Radioguided surgery in NET: First impression with Ga-68 labeled somatostatin analogues
Introduction: Neuroendocrine tumors (NET) constitute a heterogenous group of neoplasms. The development of Gallium-68-labeled somatostatin analogues, such as DOTA-NOC or DOTA-TOC, PET/CT have dramatically improved the diagnosis of neuroendocrine tumors. Surgery remains the treatment of choice for localized disease as well as metastatic disease. The aims of surgery are: improvement of symptoms, reduction of tumor mass / burden and to give better quality of life to patients. Recurrent laparotomies often lead to multiple adhesions and altered anatomy. So it is increasingly difficult for imaging physicians and surgeons to separate non-malignant from malignant tissue.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: Dr. Daniel Kaemmerer