Although female and male breast cancer share a set of commonly methylated genes, many of the studied genes are less frequently methylated in male breast cancer, pointing towards possible differences between male and female breast carcinogenesis.
Contrasting observations have been made in tumor cells, where repetitive DNA is globally demethylated, promoting genomic instability [ 16– 18], and oncogene promoters are less frequently methylated, leading to aberrant expression [ 19].
For example, hypermethylation of the death-associated protein kinase (DAPK) gene promoter was found to be significantly higher in ILC than in IDC [ 43], whereas the promoter of the Twist gene was less frequently methylated in ILC than in IDC [ 44].
This corroborated a previous study in which the TWIST1 promoter was much less frequently methylated in invasive lobular carcinomas than in invasive ductal carcinomas [6].
The majority of genes methylated in cfDNA were also methylated in tissue DNA, whereas methylation of tissue DNA was less frequently retrieved in cfDNA.
In ESCC, p16 INK4a was methylated in 40%61%% of primary tumors and was less frequently inactivated due to homozygous deletion or mutation [11], [12], whereas p14 ARF was methylated at a low frequency (13%15%%) and was mainly inactivated due to homozygous deletion [11].
As shown in Fig. 1 and Additional file 2, additional file 3, the RASSF1a promoter-CpG island was methylated in all tumor cases (29/29, 100%), but less frequently methylated in the adjacent non-cancerous liver tissues (24/29, 82.75%).
The RASSF1a was fully methylated in all tumor tissues (29/29, 100%), and less frequently methylated in corresponding non-cancerous tissue (24/29, 82.75%).
From our broad-ranging screens, we have identified GALNT9, BNC1 and CCDC8 as frequently methylated in BBM and significantly less frequently methylated in primary breast tumours (Fig. 1, Additional file 8: Figure S4).
