研究建立乳腺癌驱动因素鉴定新方法
2020-02-17 来源:小柯机器人
美国弗雷德·哈钦森癌症研究中心Slobodan Beronja研究团队揭示等位乳腺祖细胞的胚胎条形码在功能上可确定乳腺癌的驱动因素。相关论文在线发表在2020年2月13日的《细胞—干细胞》上。
研究人员表示,羊膜内慢病毒注射可以有效地转导成年乳腺的祖细胞,并以此为平台对500多个遗传性病变进行功能筛选,以了解其在肿瘤形成中的作用。靶向祖细胞在成年动物中建立了管腔和肌上皮细胞系的长期克隆,并且通过使用稳定条形码的谱系追踪。研究发现每只小鼠的乳腺都是由一定数量的大约120个早期祖细胞产生的,这些祖细胞具有一致地均等生长扩增潜力。然后,他们设计了一个体内筛选来测试乳腺癌中的遗传相互作用,确定了不仅能促进肿瘤形成也能驱动分子亚型产生的候选物。因此,该方法使得能够在乳腺上皮中快速且高通量地发现癌症驱动因素。
据了解,在完整的乳腺上皮中识别乳腺癌的临床相关驱动因素对于理解肿瘤发生至关重要,但事实证明这仍具有挑战性。
附:英文原文
Title: Embryonic Barcoding of Equipotent Mammary Progenitors Functionally Identifies Breast Cancer Drivers
Author: Zhe Ying, Slobodan Beronja
Issue&Volume: February 13, 2020
Abstract: Identification of clinically relevant drivers of breast cancers in intact mammaryepithelium is critical for understanding tumorigenesis yet has proven challenging.Here, we show that intra-amniotic lentiviral injection can efficiently transduce progenitorcells of the adult mammary gland and use that as a platform to functionally screenover 500 genetic lesions for functional roles in tumor formation. Targeted progenitorsestablish long-term clones of both luminal and myoepithelial lineages in adult animals,and via lineage tracing with stable barcodes, we found that each mouse mammary glandis generated from a defined number of ~120 early progenitor cells that expand uniformlywith equal growth potential. We then designed an in vivo screen to test genetic interactions in breast cancer and identified candidates thatdrove not only tumor formation but also molecular subtypes. Thus, this methodologyenables rapid and high-throughput cancer driver discovery in mammary epithelium.
DOI: 10.1016/j.stem.2020.01.009
Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30009-6
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