唐氏综合症（DS）是人类中最常见的染色体异常，因为额外的21号染色体拷贝而发生。DS在恶性肿瘤方面的特点独特，因为DS患者患实体肿瘤（如乳腺癌）的风险较低，但患急性髓系白血病和急性淋巴细胞白血病的风险较高。 在本研究中，我们调查了带有和不带乳腺癌的DS个体的DNA甲基化标记和表观遗传老化。我们使用Infinium Methylation EPIC BeadChip阵列分析了三体21（T21）个体而无乳腺癌的DNA甲基化模式（T21-BCF）和携带乳腺癌的DS个体（T21-BC）的DNA甲基化模式。我们的结果揭示了T21-BC患者中存在多个差异甲基化位点和区域，这些位点和区域与基因表达的改变相关。差异甲基化的CpG位点富集了与丝氨酸型肽酶活性、上皮细胞发育、GTP酶活性、双细胞紧密连接、Ras蛋白信号传导等相关的过程。另一方面，表观遗传老化加速分析显示T21-BC和T21-BCF患者之间无差异。这是第一项研究了带有和不带乳腺癌的唐氏综合症女性的DNA甲基化变化，并可以帮助揭示在DS中抗击乳腺癌的因素。版权所有 © 2023 Bejaoui, Alresheq, Durand, Vilaire-Meunier, Maillebouis, Zen, Mégarbané and Hajj.

Down Syndrome (DS) is the most common chromosome anomaly in humans and occurs due to an extra copy of chromosome 21. The malignancy profile in DS is unique, since DS patients have a low risk of developing solid tumors such as breast cancer however they are at higher risk of developing acute myeloid leukemia and acute lymphoblastic leukemia.In this study, we investigated DNA methylation signatures and epigenetic aging in DS individuals with and without breast cancer. We analyzed DNA methylation patterns in Trisomy 21 (T21) individuals without breast cancer (T21-BCF) and DS individuals with breast cancer (T21-BC), using the Infinium Methylation EPIC BeadChip array.Our results revealed several differentially methylated sites and regions in the T21-BC patients that were associated with changes in gene expression. The differentially methylated CpG sites were enriched for processes related to serine-type peptidase activity, epithelial cell development, GTPase activity, bicellular tight junction, Ras protein signal transduction, etc. On the other hand, the epigenetic age acceleration analysis showed no difference between T21-BC and T21-BCF patients.This is the first study to investigate DNA methylation changes in Down syndrome women with and without breast cancer and it could help shed light on factors that protect against breast cancer in DS.Copyright © 2023 Bejaoui, Alresheq, Durand, Vilaire-Meunier, Maillebouis, Zen, Mégarbané and Hajj.