Hypermethylation of Tumor Suppressor Genes Involved in Critical Regulatory Pathways for Developing a Blood-Based Test in Breast Cancer

Abstract

BackgroundAberrant DNA methylation patterns might be used as a biomarker for diagnosis and management of cancer patients.Methods and FindingsTo achieve a gene panel for developing a breast cancer blood-based test we quantitatively assessed the DNA methylation proportion of 248 CpG sites per sample (total of 31,248 sites in all analyzed samples) on 10 candidate genes (APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P16, P21 and TIMP3). The number of 126 samples consisting of two different cohorts was used (first cohort: plasma samples from breast cancer patients and normal controls; second cohort: triple matched samples including cancerous tissue, matched normal tissue and serum samples). In the first cohort, circulating cell free methylated DNA of the 8 tumor suppressor genes (TSGs) was significantly higher in patients with breast cancer compared to normal controls (P<0.01). In the second cohort containing triple matched samples, seven genes showed concordant hypermethylated profile in tumor tissue and serum samples compared to normal tissue (P<0.05). Using eight genes as a panel to develop a blood-based test for breast cancer, a sensitivity and specificity of more than 90% could be achieved in distinguishing between tumor and normal samples.ConclusionsOur study suggests that the selected TSG panel combined with the high-throughput technology might be a useful tool to develop epigenetic based predictive and prognostic biomarker for breast cancer relying on pathologic methylation changes in tumor tissue, as well as in circulation.

BRCA2 Promoter Hypermethylation in Sporadic Breast Cancer

“…The presenting data are promising for development of a blood-based screening method for breast cancer that relies on pathologic methylation changes, corroborating other results with different genes (Radpour et al, 2011). Further studies comparing tissue specific and blood-based methylation markers might provide valuable information as prognostic and predictive markers for breast cancer, as well as for developing novel targeted therapeutic strategies.…”

Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity

“…The methylation levels at the promotor of the tumor suppressor genes BCAP31 and OGG1 have been found to be inversely associated with survival rates and prognosis in breast cancer patients [242]. Finally, the association between promoter hyper-methylation of tumor suppressor genes and breast cancer development has also been demonstrated in other studies [243,244].…”

Recent Progress in Triple Negative Breast Cancer Research

“…In TNBC cases, hypermethylation of p16 was significantly associated tumor grade (Hafez et al, 2015) and stage of cancer (Radpour et al, 2011).…”