July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
DNA methylation patterns in Uveal Melanoma FFPE samples correlate with survival
Author Affiliations & Notes
  • Charlotte Ness
    Department of Ophthalmology, Oslo University Hospital, Oslo, Norway
    Institute of Clinical medicine, Faculty of Medicine, University of Oslo , Oslo, Norway
  • Kirankumar Katta
    Department of Ophthalmology, Oslo University Hospital, Oslo, Norway
  • Clara-Cecilie Günther
    Norwegian Computing Center, Oslo, Norway
  • Leonardo Meza-Zepeda
    Department of Tumor Biology, Institute for Cancer Research, Oslo, Norway
    Norwegian Cancer Genomics Consortium, Oslo, Norway
  • Øystein Garred
    Department of Pathology, Oslo University Hospital, Oslo, Norway
  • Theresa Kumar
    Department of Pathology, Oslo University Hospital, Oslo, Norway
  • Goran Petrovski
    Department of Ophthalmology, Oslo University Hospital, Oslo, Norway
    Institute of Clinical medicine, Faculty of Medicine, University of Oslo , Oslo, Norway
  • Morten Carstens Moe
    Department of Ophthalmology, Oslo University Hospital, Oslo, Norway
    Institute of Clinical medicine, Faculty of Medicine, University of Oslo , Oslo, Norway
  • Agate Noer
    Department of Ophthalmology, Oslo University Hospital, Oslo, Norway
  • Footnotes
    Commercial Relationships   Charlotte Ness, None; Kirankumar Katta, None; Clara-Cecilie Günther, None; Leonardo Meza-Zepeda, None; Øystein Garred, None; Theresa Kumar, None; Goran Petrovski, None; Morten Moe, None; Agate Noer, None
  • Footnotes
    Support  South-Eastern Norway Regional Health Authority (Helse Sør-Øst) project 2012104, Norwegian Cancer Society project 5808589 and supported by grants from Arthur and Odd Clausons ophthalmological fund, Aase and Knut Tønjums ophthalmological fund, Futura fund, Unifor Frimed, Norwegian Association of the Blind and Partially Sighted, Inger Holms memorial fund, Stiftelsen for fremme av kreftforskning at University of Oslo and Legat til fremme av kreftforskning.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4323. doi:
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    • Get Citation

      Charlotte Ness, Kirankumar Katta, Clara-Cecilie Günther, Leonardo Meza-Zepeda, Øystein Garred, Theresa Kumar, Goran Petrovski, Morten Carstens Moe, Agate Noer; DNA methylation patterns in Uveal Melanoma FFPE samples correlate with survival. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4323.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The present study examines correlations of DNA methylation patterns of human uveal (UM) melanoma with survival. UM is the most common primary intraocular malignancy and has a high propensity for metastatic spread. Monosomy 3 has long been known to be associated with the development of aggressive UM. The role of epigenetics in cancer research is emerging, though the epigenome of UM is less characterised. Epigenetic alterations involving DNA methylation can lead to cancer by various mechanisms, including induction of genomic instability, gene silencing and susceptibility to mutation.

Methods : Formalin fixed paraffin embedded (FFPE) samples from 24 UM patients undergoing enucleation of the eye in the period 1976-1989, were included and approved by the regional ethical committee (2013/803/REK). The inclusion was based on data from histopathology and from the Norwegian Cancer Registry and the Norwegian Cause of Death Registry. Survival cut-off: early relapse ≤5 years, late relapse ≥10 years and “Ctrl”/no relapse ≥17 years. DNA was isolated from the FFPE samples and further bisulphite converted and restored according to Illumina`s recommendations. Bisulphite converted DNA was then run on The Infinium HumanMethylation450 BeadChip assay (HM-450K). Bioinformatics analyses were conducted in R statistical software, including analysis of copy number variation (CNV). RNA was isolated from the FFPE samples and Clariom D arrays were used to verify changes in gene expression correlated to changes in methylation.

Results : Cluster analysis was performed using unsupervised hierarchical clustering. Our data shows subclustering correlated with survival and mortality, additionally our data provides insight of epigenetically deregulated (hypo/hyper methylated) genes and CNV. After limma analysis of subcluster, 4 samples of “Ctrl”/no relapse compared to 4 samples of early relapse, unraveled 335 significant probes (p-value≤0.05) with the potential of increasing our knowledge about the underlying mechanisms of UM.

Conclusions : The methylation profile of a given cancer can elucidate therapeutic targets, reveal biomarkers for early detection or identify high risk tumours. This is to our knowledge the first report of methylation
changes in FFPE samples derived from UMs correlated to survival.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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