English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Breast carcinogenesis is a multistep process involving genetic and epigenetic changes. Tumor tissues are frequently characterized by gene-specific hypermethylation and global DNA hypomethylation. Aberrant DNA methylation levels have, however, not only been found in tumors, but also in tumor-surrounding tissue appearing histologically normal. This phenomenon is called field cancerization. Knowledge of the existence of a cancer field and its spread are of clinical relevance. If the tissue showing pre-neoplastic lesions is not removed by surgery, it may develop into invasive carcinoma.    Methods  We investigated the prevalence of gene-specific and global DNA methylation changes in tumor-adjacent and tumor-distant tissues in comparison to tumor tissues from the same breast cancer patients ( n  = 18) and normal breast tissues from healthy women ( n  = 4). Methylation-sensitive high resolution melting (MS-HRM) analysis was applied to determine methylation levels in the promoters of  APC ,  BRCA1 ,  CDKN2A (p16) ,  ESR1 ,  HER2/neu  and  PTEN,  in  CDKN2A  exon 2 and in LINE-1, as indicator for the global DNA methylation extent. The methylation status of the  ESR2  promoter was determined by pyrosequencing.    Results  Tumor-adjacent and tumor-distant tissues frequently showed pre-neoplastic gene-specific and global DNA methylation changes. The  APC  promoter ( p  = 0.003) and exon 2 of  CDKN2A  ( p  < 0.001) were significantly higher methylated in tumors than in normal breast tissues from healthy women. For both regions, significant differences were also found between tumor and tumor-adjacent tissues ( p  = 0.001 and  p  < 0.001, respectively) and tumor and tumor-distant tissues ( p  = 0.001 and  p  < 0.001, respectively) from breast cancer patients. In addition, tumor-adjacent ( p  = 0.002) and tumor-distant tissues ( p  = 0.005) showed significantly higher methylation levels of  CDKN2A  exon 2 than normal breast tissues serving as control. Significant correlations were found between the proliferative activity and the methylation status of  CDKN2A  exon 2 in tumor ( r  = −0.485,  p  = 0.041) and tumor-distant tissues ( r  = −0.498,  p  = 0.036).    Conclusions  From our results we can conclude that methylation changes in  CDKN2A  exon 2 are associated with breast carcinogenesis. Further investigations are, however, necessary to confirm that hypermethylation of  CDKN2A  exon 2 is associated with tumor proliferative activity.

Hypermethylation of CDKN2A exon 2 in tumor, tumor-adjacent and tumor-distant tissues from breast cancer patients