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探究腫瘤細胞的起源及演化對理解癌癥的發(fā)生、復(fù)發(fā)以及對后續(xù)腫瘤的預(yù)防和治療至關(guān)重要。腫瘤細胞起源于正常細胞內(nèi)突變的積累，然后在微環(huán)境、手術(shù)、放化療等不同的選擇壓力下，經(jīng)歷多個階段的演化。對演化過程的研究能夠揭示癌癥的發(fā)生、發(fā)展規(guī)律，鑒定癌細胞起源及演化相關(guān)的基因組事件，進而為治療腫瘤提供新的藥物靶點。研究組前期通過開發(fā)高通量單細胞DNA測序技術(shù)（Arc-well）、單細胞進行空間位置（或樣本信息）標(biāo)記的方法SNuBar以及多種基于高通量測序的低頻突變檢測方法（o2n-seq, Droplet-CirSeq, Oseq和EasyMF）系統(tǒng)研究了乳腺癌原發(fā)到復(fù)發(fā)的克隆演化關(guān)系，揭示了原發(fā)到復(fù)發(fā)癌的克隆演化模型，鑒定了與乳腺癌復(fù)發(fā)相關(guān)的基因組變異事件，為后續(xù)乳腺癌的治療提供了目標(biāo)靶點。課題組將繼續(xù)通過開發(fā)高通量單細胞多組學(xué)測序技術(shù)、空間組學(xué)測序技術(shù)等來回答關(guān)于腫瘤細胞起源和演化的問題：如體細胞突變?nèi)绾螌?dǎo)致腫瘤的發(fā)生，導(dǎo)致腫瘤起源的上皮細胞亞型，腫瘤起始細胞空間定位、多組學(xué)表征及其與微環(huán)境互作關(guān)系，衰老與腫瘤的關(guān)系等。

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