DNA Methylation Profiling of Trisomy 21 Patients With Breast Cancer

Down syndrome (DS), also called trisomy 21 (T21) occurs due to an extra full chromosome 21 and is the most common chromosomal anomaly in humans. DS is linked to various phenotypical features, developmental retardation, and medical complications. The malignancy profile in DS is unique, as DS patients have significant lower frequency of developing solid tumors compared to the normal population. Breast cancer (BC), for example, is almost absent in DS patients with a frequency of 0.7% compared to 12.5% in the general population. Epigenetic dysregulation is a driving factor of breast cancer progression. Thus, we hypothesized that novel epigenetic factors are associated with the lower breast cancer frequency observed in women with T21. In order to test our hypothesis, we analyzed the methylation profile of T21 women with breast cancer (T21-BC), T21 women without breast cancer (T21-BCF), and women with normal karyotype diagnosed with breast cancer (NK-BC, n=75). Furthermore, the gene expression changes previously reported in the transcriptomic study performed by Mégarbané et al. were compared to the differentially methylated sites/regions from this study. As a result, on the regional level 5 genes that are differentially expressed in the RNA seq data were identified to have differentially methylated promoters in T21-BCF patients in the context of T21-BC Vs T21-BCF. In addition, an enrichment for the Wnt signalling pathway was observed for the 564 CpG sites differentially methylated and corresponding to differentially expressed genes in the T21-BC vs. T21-BCF analysis.