scholarly journals Whole genome methylation analysis of non-dysplastic Barretts oesophagus that progresses to invasive cancer

2017 ◽  
Author(s):  
MP Dilworth ◽  
T Nieto ◽  
JD Stockton ◽  
C Whalley ◽  
L Tee ◽  
...  

ABSTRACTObjectiveTo investigate differences in methylation between patients with non-dysplastic Barretts’ oesophagus who progress to invasive adenocarcinoma and those that do not.DesignA whole genome methylation interrogation using the Illumina HumanMethylation 450 array of patients with non-dysplastic Barrett’s Oesophagus who either develop adenocarcinoma or remain static, with validation of findings by bisulfite pyrosequencingResultsIn total, 12 patients with “progressive” vs. 12 with “non-progressive” non-dysplastic Barrett’s oesophagus were analysed via methylation array. Fourty-four methylation markers were identified that may be able to discriminate between non-dysplastic Barrett’s Oesophagus that either progress to adenocarcinoma or remain static. Hypomethylation of the recently identified tumour supressorOR3A4(probe cg09890332) validated in a separate cohort of samples (median methylation in progressors = 67.8% vs. 96.7% in non-progressors,p=0.0001, z = 3.85, Wilcoxon rank sum test) and was associated with the progression to adenocarcinoma. There were no differences in copy number between the two groups, but a global trend towards hypomethylation in the progressor group was observed.ConclusionHypomethylation ofOR3A4has the ability to risk stratify the patient with non-dysplastic Barrett’s Oesophagus and may form the basis of a future surveillance program.


2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Yinfeng Zhang ◽  
Sai-Kam Li ◽  
Kevin Yi Yang ◽  
Minghua Liu ◽  
Nelson Lee ◽  
...  


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4566-4566 ◽  
Author(s):  
Jenny J. Kim ◽  
Mariette Labots ◽  
Luigi Marchionni ◽  
Shahnaz Begum ◽  
Gerrit A. Meijer ◽  
...  

4566 Background: There exists a significant heterogeneity in the clinical response to sunitinib among pts treated for mRCC and, thus, a biomarker which would predict pts’ response up front would be an invaluable tool in the clinical management of these pts. In this regard, whole genome methylation array was performed between 2 extreme groups: sunitinib responders (RES) and non-responders (NRES) to identify differentially methylated genes between these subsets of pts. Methods: mRCC pts who received sunitinib therapy with available frozen nephrectomy tissues (stored at -80°C) and clinical data were identified. RES were identified as pts with progression free survival (PFS) of > or =11 months (mos) and NRES as those with PFS < or = 3 mos. After DNA extraction and quality assurance according to standard protocol, whole genome methylation array was performed using Infinium Humanmethylation450 BeadChip Kit - Illumina. Data normalization was achieved by subset-quantile within array normalization (PMID: 22703947). Differentially methylated regions were identified using logit transformed Beta values, using an F-test after shrinking variance via empirical Bayes (PMID: 21118553). Results: Total of 13 pts who received sunitinib therapy with available frozen nephrectomy tissues were identified. Of the 13, 5 pts qualified for each RES and NRES cohort as described in methods section. All pts in RES group had clear cell subtype. Two pts of the NRES group were of non-clear cell subtype. The QC plots showed that all arrays were successful. For RES vs. NRES, one genomic location, DENND2D, was significantly hypermethylated in the RES group with a false discovery rate (FDR) of <10%. DENND2D has been identified as a tumor suppressor-like gene in non-small cell lung cancer and melanoma cell lines in the recent past. Conclusions: In this study, DENND2D was significantly hypermethylated in sunitinib RES compared to NRES among mRCC pts. Data analysis with a less stringent FDR is also being pursued. Technical validation as well as clinical validation of DENND2D utilizing a larger pt cohort are ongoing.



2013 ◽  
Vol 14 (1) ◽  
Author(s):  
Rada Staneva ◽  
Blaga Rukova ◽  
Savina Hadjidekova ◽  
Desislava Nesheva ◽  
Olga Antonova ◽  
...  


2001 ◽  
Vol 120 (5) ◽  
pp. A415-A415
Author(s):  
R FITZGERALD ◽  
B ONWUEGBUSI ◽  
G DEPAULO ◽  
R FEAKINS ◽  
L MCKINNEY ◽  
...  




2020 ◽  
Author(s):  
Fabrice Caillol ◽  
Arthur Falque ◽  
Margherita Pizzicannella ◽  
Christian Pesenti ◽  
Jean Philippe Ratone ◽  
...  


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