The objective of the present study was to evaluate the epigenetic changes occurring in early stages of breast cancer. The present study investigated the methylation profile of the ATM, p14 ARF and p16 INK4a promoters in total blood and plasma cell-free DNA (cfDNA) from women with impalpable breast lesions compared with in total blood of a control cohort of women without breast lesions. The samples were evaluated using the methylation-specific PCR method. The Fisher's exact test was used to evaluate statistical significance between the methylation and clinical variables. A total of 111 women were evaluated, including 56 women with impalpable breast cancer (39/56 also had paired plasma cfDNA) and 55 women in the control cohort (55 blood DNA). For blood DNA from women with malignant impalpable breast lesions, p16 INK4a exhibited the greatest percentage of methylation (48%), followed by ATM (37.5%) and p14 ARF (27%) promoters, regardless of age variation. For plasma cfDNA, the methylation rates for ATM, p14 ARF and p16 INK4a were 26, 26 and 10%, respectively. The methylation rates for the blood DNA of controls were the lowest for ATM (9%), p14 ARF (7%) and p16 INK4a (7%). The women with impalpable breast lesions (benign and malignant lesions) exhibited the highest methylation rate, regardless of age, compared with the paired plasma cfDNA and controls. This epigenetic change was statistically significant for the promoters of ATM (P=0.009) and p16 INK4a (P=0.001) (impalpable breast lesions vs. control). The present study demonstrated that epigenetic changes occurring in the ATM and CDKN2A genes detectable in liquid biopsy were associated with the development of impalpable breast lesions.

Abstract. Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis, different degrees of cellular dysplasia, and increased risk of progression to acute myeloid leukemia. International Prognostic Scoring System is the gold standard for MDS classification; however, patients exhibiting different clinical behaviors often coexist in the same group, indicating that the currently available scoring systems are insufficient. The genes that have recently been identified as mutated in MDS, including additional sex combs like 1, transcriptional regulator (ASXL1), tumor protein p53 (TP53), and KRAS proto-oncogene and GTPase (KRAS)/NRAS proto-oncogene, GTPase (NRAS), may contribute to a more comprehensive classification, as well as to the prognosis and progression of the disease. In the present study, the mutations in the ASXL1, TP53 and NRAS/KRAS genes in 50 patients were evaluated by sequencing genomic bone marrow DNA. Nine patients (18%) presented with at least one type of mutation. Mutations in TP53 were the most frequent in six patients (12%), followed by ASXL1 in two patients (4%) and NRAS in one patient (2%). The nine mutations were detected in patients with low-and high-risk MDS. The screening of mutations in MDS cases contributes to the application of personalized medicine.