美国德克萨斯大学Nicholas Navin研究组发现，正常乳腺组织中存在少数非整倍体上皮细胞群体。相关论文于2024年11月20日在线发表在《自然》杂志上。

研究人员表示，非整倍体上皮细胞在乳腺癌中较为常见；然而，它们在正常乳腺组织中的存在尚不完全明了。

为了解决这个问题，研究人员应用单细胞DNA测序对来自49名健康女性的83206个乳腺上皮细胞进行了拷贝数变异分析，并对19名女性的样本进行了单细胞DNA测序和转座酶可接近染色质测序联合检测。

数据表明，所有女性的乳腺组织中都存在少数非整倍体上皮细胞（中位数3.19%），并且随着年龄的增长，其比例增加。许多非整倍体上皮细胞（中位数82.22%）经历了克隆扩增，并且携带有类似侵袭性乳腺癌的拷贝数变异（1q增益；10q、16q和22q缺失）。

联合检测分析表明，这些非整倍体细胞主要与两种腔道上皮谱系相关，空间定位分析显示它们定位于具有正常组织学的导管和小叶结构中。总体而言，这些数据表明，即便是健康女性，其乳腺组织中也存在少数非整倍体上皮细胞的克隆扩增。

附：英文原文 

Title: Normal breast tissues harbour rare populations of aneuploid epithelial cells

Author: Lin, Yiyun, Wang, Junke, Wang, Kaile, Bai, Shanshan, Thennavan, Aatish, Wei, Runmin, Yan, Yun, Li, Jianzhuo, Elgamal, Heba, Sei, Emi, Casasent, Anna, Rao, Mitchell, Tang, Chenling, Multani, Asha S., Ma, Jin, Montalvan, Jessica, Nagi, Chandandeep, Winocour, Sebastian, Lim, Bora, Thompson, Alastair, Navin, Nicholas

Issue&Volume: 2024-11-20

Abstract: Aneuploid epithelial cells are common in breast cancer1,2; however, their presence in normal breast tissues is not well understood. To address this question, we applied single-cell DNA sequencing to profile copy number alterations in 83,206 epithelial cells from the breast tissues of 49 healthy women, and we applied single-cell DNA and assay for transposase-accessible chromatin sequencing co-assays to the samples of 19 women. Our data show that all women harboured rare aneuploid epithelial cells (median 3.19%) that increased with age. Many aneuploid epithelial cells (median 82.22%) in normal breast tissues underwent clonal expansions and harboured copy number alterations reminiscent of invasive breast cancers (gains of 1q; losses of 10q, 16q and 22q). Co-assay profiling showed that the aneuploid cells were mainly associated with the two luminal epithelial lineages, and spatial mapping showed that they localized in ductal and lobular structures with normal histopathology. Collectively, these data show that even healthy women have clonal expansions of rare aneuploid epithelial cells in their breast tissues.

DOI: 10.1038/s41586-024-08129-x

Source: https://www.nature.com/articles/s41586-024-08129-x