研究建立乳腺癌驅(qū)動(dòng)因素鑒定新方法
2020-02-17
來(lái)源：小柯機(jī)器人
美國(guó)弗雷德·哈欽森癌癥研究中心Slobodan Beronja研究團(tuán)隊(duì)揭示等位乳腺祖細(xì)胞的胚胎條形碼在功能上可確定乳腺癌的驅(qū)動(dòng)因素。相關(guān)論文在線發(fā)表在2020年2月13日的《細(xì)胞—干細(xì)胞》上。
研究人員表示，羊膜內(nèi)慢病毒注射可以有效地轉(zhuǎn)導(dǎo)成年乳腺的祖細(xì)胞，并以此為平臺(tái)對(duì)500多個(gè)遺傳性病變進(jìn)行功能篩選，以了解其在腫瘤形成中的作用。靶向祖細(xì)胞在成年動(dòng)物中建立了管腔和肌上皮細(xì)胞系的長(zhǎng)期克隆，并且通過(guò)使用穩(wěn)定條形碼的譜系追蹤。研究發(fā)現(xiàn)每只小鼠的乳腺都是由一定數(shù)量的大約120個(gè)早期祖細(xì)胞產(chǎn)生的，這些祖細(xì)胞具有一致地均等生長(zhǎng)擴(kuò)增潛力。然后，他們?cè)O(shè)計(jì)了一個(gè)體內(nèi)篩選來(lái)測(cè)試乳腺癌中的遺傳相互作用，確定了不僅能促進(jìn)腫瘤形成也能驅(qū)動(dòng)分子亞型產(chǎn)生的候選物。因此，該方法使得能夠在乳腺上皮中快速且高通量地發(fā)現(xiàn)癌癥驅(qū)動(dòng)因素。
據(jù)了解，在完整的乳腺上皮中識(shí)別乳腺癌的臨床相關(guān)驅(qū)動(dòng)因素對(duì)于理解腫瘤發(fā)生至關(guān)重要，但事實(shí)證明這仍具有挑戰(zhàn)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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