title: Differential DNA methylome profiling of nonfunctioning pituitary adenomas suggesting tumour invasion is correlated with cell adhesion.
abstract: Global and gene-specific changes to the epigenome are hallmarks of most tumours including those of pituitary origin, and this fact might offer important clues about diagnostic and therapeutic applications. We performed global DNA methylation screening with 6 invasive and 6 noninvasive nonfunctioning pituitary adenomas (PA) to investigate whether DNA methylation was associated with the invasion of nonfunctioning pituitary adenomas. An additional seven PAs were included as an independent cohort to validate the initial results. Five thousand nine hundred thirty-one CpGs were selected (△β ≥0.15 and p value ≤0.01) as differentially methylated sites (DMSs). The hypomethylated DMSs in the invasive PAs were significantly more than the hypermethylated sites. Cluster analysis of 339 CpGs (△β ≥0.25 and p value ≤0.001) demonstrated a complete distinction between the invasive and noninvasive nonfunctioning groups. GO analysis of the three hundred seven corresponding genes shown they were involved in homophilic cell adhesion, cell-cell adhesion, cell adhesion and biological adhesion. The mRNA expression of GALNT9 which contain a validated DMS was significantly downregulated in invasive group. Our findings indicate that the differential DNA methylome profiling of invasive and noninvasive nonfunctioning PAs suggesting tumour invasion is correlated with cell adhesion.
authors.affiliation: Department of Neurosurgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Institute of Developmental Biology and Birth Defect, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Xinyao
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.|Shanghai Key Lab of Medical Image Computing and Computer Assisted Intervention, Fudan University, Shanghai, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xie
authors.affiliation: Department of Neurosurgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China. xzzhao@fudan.edu.cn.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. Xiaobiao_zhang@163.com.|Shanghai Key Lab of Medical Image Computing and Computer Assisted Intervention, Fudan University, Shanghai, China. Xiaobiao_zhang@163.com.
authors.forename: Xiaobiao
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D002448:Cell Adhesion / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D017350:N-Acetylgalactosaminyltransferases; C580736:GALNT9 protein, human
keywords: Cell adhesion; DNA methylation; Invasion; Nonfunctioning pituitary adenomas