DNA methylation epigenotypes in breast cancer molecular subtypes
 

http://breast-cancer-research.com/co...df/bcr2721.pdf

"One of the most interesting aspects of the validation study was to observe that while the microarray analysis showed no specific methylation profile HER2 overexpressing tumors, the validation study (carried out in a larger sample size) demonstrated that HER2 overexpressing tumors (luminal B and ERBB2+ tumors) had a common methylation profile." (p. 11)

" Specifically, basal-like tumors were inversely associated to NPY, FGF2, HS3ST2, RASSF1 and Let-7a markers hypermethylation (sensibility 75%, specificity 95% and FDR: 0.17) whereas HER2 overexpressing subtypes were strongly correlated to NPY, FGF2, HS3ST2, RASSF1 and Let-7a hypermethylation (sensibility 74%, specificity 80% and FDR: 0.18). "(p.12)

"As previously suggested, we have found that basal-like, ERBB2+, luminal A and luminal B molecular subtypes displayed specific methylation profiles. Specifically, HER2-enriched breast tumors (ERBB2+ and luminal B) were associated with the hypermethylation of several genes related to cancer development (Table 3). . . In addition, Terada et al [35] have recently found that frequent CpG islands methylation is highly associated with HER2 amplification." (p.13)

"Finally, epignetic therapy, including the use of demethylating agents and histone deacetylation inhibitors is now in clinical trials for myelodysplastic syndrome, leukemia and ovarian and lung cancers [21]. Recent studies have suggested that cotreatment of DNA methylation inhibitors and histone deacetylases might be an effective form of epigenetic therapy for breast cancer, as the interplay observed between DNA methylation and histone modifications can result in synergystic induction of tumor suppresor genes [21,44]. Thus, there is a possibility that epigenetic therapy could play an important role in the immediate furture of breast cancer treatment. The information of subtype-specific methylation profiles described in the present study, might promote a better understanding of the epigenetic regulation mechanisms in breast cancer, thereby contributing to the improvement of epigenetic therapy." (p.15)

Hopeful