Genome-wide methylation analyses identifies Non-coding RNA genes dysregulated in breast tumours that metastasise to the brain

Pangeni, Rajendra P, Olivaries, Ivonne, Huen, David, Buzatto, Vannessa C, Dawson, Timothy P, Ashton, Katherine M, Davis, Charles, Brodbelt, Andrew R, Jenkinson, Michael D ORCID: 0000-0003-4587-2139, Bieche, Ivan
et al (show 5 more authors) (2022) Genome-wide methylation analyses identifies Non-coding RNA genes dysregulated in breast tumours that metastasise to the brain. SCIENTIFIC REPORTS, 12 (1). 1102-.

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Brain metastases comprise 40% of all metastatic tumours and breast tumours are among the tumours that most commonly metastasise to the brain, the role that epigenetic gene dysregulation plays in this process is not well understood. We carried out 450 K methylation array analysis to investigate epigenetically dysregulated genes in breast to brain metastases (BBM) compared to normal breast tissues (BN) and primary breast tumours (BP). For this, we referenced 450 K methylation data for BBM tumours prepared in our laboratory with BN and BP from The Cancer Genome Atlas. Experimental validation on our initially identified genes, in an independent cohort of BP and in BBM and their originating primary breast tumours using Combined Bisulphite and Restriction Analysis (CoBRA) and Methylation Specific PCR identified three genes (RP11-713P17.4, MIR124-2, NUS1P3) that are hypermethylated and three genes (MIR3193, CTD-2023M8.1 and MTND6P4) that are hypomethylated in breast to brain metastases. In addition, methylation differences in candidate genes between BBM tumours and originating primary tumours shows dysregulation of DNA methylation occurs either at an early stage of tumour evolution (in the primary tumour) or at a later evolutionary stage (where the epigenetic change is only observed in the brain metastasis). Epigentic changes identified could also be found when analysing tumour free circulating DNA (tfcDNA) in patient's serum taken during BBM biopsies. Epigenetic dysregulation of RP11-713P17.4, MIR3193, MTND6P4 are early events suggesting a potential use for these genes as prognostic markers.

Item Type: Article
Uncontrolled Keywords: Brain, Humans, Breast Neoplasms, Brain Neoplasms, Neoplasm Metastasis, Receptors, Cell Surface, MicroRNAs, DNA, RNA, Untranslated, Prognosis, Gene Expression Profiling, DNA Methylation, Gene Expression, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Databases, Genetic, Female, Promoter Regions, Genetic, Epigenomics, Transcriptome, Biomarkers, Tumor
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 27 May 2022 08:33
Last Modified: 18 Jan 2023 21:00
DOI: 10.1038/s41598-022-05050-z
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