乳腺導(dǎo)管原位癌又稱零期乳腺癌，屬于最早期的乳腺癌,，大部分患者僅需接受小手術(shù)簡(jiǎn)單切除,，術(shù)后即使不接受放化療或內(nèi)分泌治療，也不會(huì)復(fù)發(fā)或惡化為乳腺浸潤癌,，少數(shù)患者術(shù)后數(shù)年甚至數(shù)十年仍然可能復(fù)發(fā)或惡化,，需要積極治療、密切隨訪,。了解乳腺導(dǎo)管原位癌復(fù)發(fā)惡化前的基因組變化,，有助于確定哪些患者將來復(fù)發(fā)惡化風(fēng)險(xiǎn)較高或較低，以避免治療不足或過度,。不過,，對(duì)于數(shù)年甚至數(shù)十年前福爾馬林固定石蠟包埋的腫瘤組織，目前仍然難以進(jìn)行基因組分析,。 2023年8月15日,，全球自然科學(xué)三大旗艦期刊之一、美國《細(xì)胞》正刊在線發(fā)表美國德克薩斯大學(xué)MD安德森癌癥中心,、杜克大學(xué)醫(yī)學(xué)院,、貝勒醫(yī)學(xué)院、英國倫敦大學(xué)國王學(xué)院蓋伊癌癥中心,、英國癌癥研究基金會(huì),、荷蘭癌癥研究院、范列文虎克醫(yī)院,、荷蘭癌癥基金會(huì),、萊頓大學(xué)醫(yī)學(xué)中心的研究報(bào)告，利用一種新方法可以對(duì)數(shù)年甚至數(shù)十年前福爾馬林固定石蠟包埋的腫瘤組織成千上萬個(gè)細(xì)胞進(jìn)行DNA測(cè)序,。 該研究通過分析4萬330個(gè)單細(xì)胞對(duì)該方法進(jìn)行驗(yàn)證,，這些細(xì)胞來自細(xì)胞系,、冷凍組織以及已經(jīng)儲(chǔ)存3～31年的23個(gè)乳腺腫瘤福爾馬林固定石蠟包埋標(biāo)本。 對(duì)10例患者的乳腺導(dǎo)管原位癌及其2～16年后復(fù)發(fā)癌分析表明,，許多原發(fā)的乳腺導(dǎo)管原位癌已經(jīng)存在全基因組倍增和克隆多樣化,，并且與復(fù)發(fā)癌的持續(xù)亞克隆基因組譜系相同。 進(jìn)化分析表明,，該隊(duì)列大多數(shù)乳腺導(dǎo)管原位癌病例經(jīng)歷了進(jìn)化瓶頸,，并進(jìn)一步確定了復(fù)發(fā)相關(guān)持續(xù)亞克隆的染色體畸變。 因此,，該研究結(jié)果表明,，該方法可以對(duì)存檔福爾馬林固定石蠟包埋的成千上萬個(gè)細(xì)胞進(jìn)行大規(guī)模單細(xì)胞DNA并行測(cè)序，開辟了對(duì)世界各地收集和存檔的大量臨床福爾馬林固定石蠟包埋組織進(jìn)行研究的新途徑,，可用于研究癌癥和其他人類疾病的長期臨床結(jié)局?jǐn)?shù)據(jù),。此外，該方法還可以對(duì)未固定的組織（新鮮或冷凍）進(jìn)行大規(guī)模單細(xì)胞DNA并行測(cè)序,，并對(duì)許多現(xiàn)有單細(xì)胞DNA并行測(cè)序方法進(jìn)行基準(zhǔn)測(cè)試,，從而提高數(shù)據(jù)質(zhì)量。最重要的是,，該研究發(fā)現(xiàn)乳腺導(dǎo)管原位癌復(fù)發(fā)或浸潤前幾年甚至十幾年就已存在某些基因組變化,，有助于確定哪些患者將來復(fù)發(fā)惡化風(fēng)險(xiǎn)較高或較低，以避免治療不足或治療過度,，故有必要進(jìn)一步開展大樣本臨床研究進(jìn)行驗(yàn)證,。Cell. 2023 Aug 15. IF: 64.5Archival single-cell genomics reveals persistent subclones during DCIS progression.Kaile Wang, Tapsi Kumar, Junke Wang, Darlan Conterno Minussi, Emi Sei, Jianzhuo Li, Tuan M. Tran, Aatish Thennavan, Min Hu, Anna K. Casasent, Zhenna Xiao, Shanshan Bai, Lei Yang, Lorraine M. King, Vandna Shah, Petra Kristel, Carolien L. van der Borden, Jeffrey R. Marks, Yuehui Zhao, Amado J. Zurita, Ana Aparicio, Brian Chapin, Jie Ye, Jianjun Zhang, Don L. Gibbons, Grand Challenge PRECISION Consortium, Ellinor Sawyer, Alastair M. Thompson, Andrew Futreal, E. Shelley Hwang, Jelle Wesseling, Esther H. Lips, Nicholas E. Navin.UT MD Anderson Cancer Center, Houston, TX, USA; MD Anderson UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA; Duke University School of Medicine, Durham, NC, USA; Baylor College of Medicine, Houston, TX, USA; Guy's Cancer Centre, King's College London, London, UK; Grand Challenge PRECISION Consortium, Cancer Research UK; Netherlands Cancer Institute, Amsterdam, the Netherlands; KWF Dutch Cancer Foundation; Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; Leiden University Medical Center, Leiden, the Netherlands.- Arc-well is a high-throughput single-cell DNA-seq method for archival FFPE tissues
- Arc-well reliably profiled thousands of cells from 27 FFPE tissues archived for years
- Persistent subclones from DCIS and matched recurrences were identified
- Most DCIS cases in this cohort underwent an evolutionary bottleneck
Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. Here, we developed Arc-well, a high-throughput single-cell DNA-sequencing method that is compatible with FFPE materials. We validated our method by profiling 40,330 single cells from cell lines, a frozen tissue, and 27 FFPE samples from breast, lung, and prostate tumors stored for 3-31 years. Analysis of 10 patients with matched DCIS and cancers that recurred 2-16 years later show that many primary DCIS had already undergone whole-genome doubling and clonal diversification and that they shared genomic lineages with persistent subclones in the recurrences. Evolutionary analysis suggests that most DCIS cases in our cohort underwent an evolutionary bottleneck, and further identified chromosome aberrations in the persistent subclones that were associated with recurrence.KEYWORDS: Arc-well, single-cell DNA sequencing, FFPE material, archival samples, ductal carcinoma in situ recurrence, tumor evolution, breast cancer, premalignanciesDOI: 10.1016/j.cell.2023.07.024
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