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Differential DNA methylome profiling of nonfunctioning pituitary adenomas suggesting tumour invasion is correlated with cell adhesion

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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.

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Abbreviations

CGI:

CpG islands

Chr:

Chromosomes

DMS:

Differentially methylated sites

PA:

Pituitary adenomas

TSS:

Transcription start site

TSS200:

Within 200 bps of a TSS

TSS1500:

Within 1500 bps of a TSS

1st exon:

The first exon

450k:

Infinium Human Methylation450 BeadChip

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Acknowledgements

We gratefully acknowledge the contributions of all named authors to this work and the kind cooperation the pathologist Yingyong Hou, the director of the department of pathology in Zhongshan Hospital, for the confirmation of pathological diagnoses. This work was supported by Foundation of Shanghai Science and Technology Commission (134119a1202) and Shanghai Municipal Hospitals’ Rising and Leading Technology Program (SHDC12013121).

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    Authors and Affiliations

    1. Department of Neurosurgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China

      Ye Gu, Fan Hu, Yong Yu, Tao Xie, Yuying Huang & Xiaobiao Zhang

    2. Shanghai Key Lab of Medical Image Computing and Computer Assisted Intervention, Fudan University, Shanghai, China

      Fan Hu & Xiaobiao Zhang

    3. Institute of Developmental Biology and Birth Defect, Institutes of Biomedical Sciences, Fudan University, Shanghai, China

      Xinyao Zhou

    4. Children’s Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China

      Xinzhi Zhao

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    1. Ye Gu
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    Correspondence to Xinzhi Zhao or Xiaobiao Zhang.

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    Y. Gu and X. Zhou contributed equally to this article.

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    Gu, Y., Zhou, X., Hu, F. et al. Differential DNA methylome profiling of nonfunctioning pituitary adenomas suggesting tumour invasion is correlated with cell adhesion. J Neurooncol 129, 23–31 (2016). https://doi.org/10.1007/s11060-016-2139-4

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    • DOI: https://doi.org/10.1007/s11060-016-2139-4

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