Table 1 Genes frequently methylated in breast to brain metastases. Twenty-one genes are frequently methylated in brain metastases (n = 15) of which 18 genes are also frequently methylated in primary breast tumours (n = 20). Three genes, CCDC8, BNC1 and GALNT9 (highlighted in grey), are infrequently methylated in primary breast tumours. These genes were further analysed in 20 primary breast samples (n = 40 in total) and 15 breast to brain metastases (n = 30 in total)
Gene symbol | Accession | Gene name | % of metastatic tumours methylated | Function |
|---|---|---|---|---|
CLDN18 | NM_016369.3 | Claudin 18 | 100 | Intercellular adhesion molecule responsible for tight junction strand formation [77] |
KRT85 | NM_002283.3 | Keratin 85 | 100 | Component of intermediate filament in epithelial cells contributing to cell-cell adhesion [78–80] |
MIR127 | NR_029696.1 | microRNA 127 | 100 | Regulator of cell proliferation and senescence [81] |
MIR433 | NR_029966.1 | microRNA 433 | 100 | Deregulated in gastric cancer, regulator of cell migration and drug response [82, 83] |
HOXD3 | NM_006898.4 | HomeoboxD3 | 100 | Proangiogenic transcription factor [84] |
MIR23B | NR_029664.1 | microRNA 23b | 92 | Involved in cytoskeleton modelling, motility and metastasis [85–88] |
CCDC8 | NM_032040.4 | Coil coiled domain containing 8 | 73 | Mutated in patients with 3 M syndrome [70]. Loss is associated with genomic instability and aneuploidy [75]. |
KRT83 | NM_002282.3 | Keratin 83 | 84 | Component of intermediate filament, contributes to cell to cell adhesion [78, 80] |
HOXB13 | NM_006361.5 | Homeobox B13 | 80 | TSG for prostate cancer, inhibits androgen mediated signalling [89] |
ABCB1 | NM_000927.4 | ATP-binding cassette sub-family B member 1 | 80 | Controls efflux of substances across plasma membranes, associated with multidrug resistance [90] |
PENK | NM_006211.3 | Proenkephalin | 80 | Promotes RNA splicing in osteoblasts and neural cells, plays role in bone development [91] |
MST1R | NM_002447.2 | Macrophage stimulating 1 receptor | 78 | Involved in intracellular signalling cascades leading to cellular growth, motility and invasion [92] |
BNC1 | NM_001717.3 | Basonuclin 1 | 71 | Zink finger transcription factor, regulator of EMT [68] |
PCDH8 | NM_002590.3 | Procadhern 8 | 73 | Helps in cell to cell adhesion [93] |
STAT3 | NM_139276.2 | Signal transducer and activator of transcription 3 | 67 | Involved in embryonic stem cell regulation, somatic cell growth [94–96] |
BVES | NM_007073.4 | Blood vessel epicardial substance | 64 | Involved in inter-cellular interaction and cell adhesion [97] |
TNFRSF10D | NM_003840.4 | Tumour Necrosis Factor receptor superfamily 10 D | 60 | Member of TNF (Tumour Necrosis Factor) receptor superfamily, promotes apoptosis in cancer cells [98] |
CLDN6 | NM_021195.4 | Claudin 6 | 55 | Intercellular adhesion molecules responsible for tight junction strand formation, its epigenetic silencing is associated with migration and invasiveness of breast cancer [77, 99] |
HOXD10 | NM_002148.3 | Homeobox D10 | 55 | Maintain epithelial cell plasticity and contributes to stability of extracellular matrix [100] |
GALNT9 | NM_001122636.1 | N-acetyl galactosaminyl transferase 9 | 55 | |
WIF1 | NM_007191.4 | Wnt inhibitory factor-1 gene | 53 |