Transcriptome and genome evolution during HER2-amplified breast neoplasia.
Transcriptome and genome evolution during HER2-amplified breast neoplasia.
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DOI：
10.1186/s13058-021-01451-6
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发表时间：
2021-07-15
期刊：
影响因子：
--
通讯作者：
West R
中科院分区：
文献类型：
--
作者：
Lu P;Foley J;Zhu C;McNamara K;Sirinukunwattana K;Vennam S;Varma S;Fehri H;Srivastava A;Zhu S;Rittscher J;Mallick P;Curtis C;West R
致癌驱动因子的获得是癌症进展的关键特征。对于一些癌症，很明显，某些遗传驱动因素在瘤形成早期发生，而其他则发生在晚期。为什么选择这些驱动因素以及这些变化如何改变肿瘤的适应性还不太清楚。在这里，我们使用空间定向的基因组方法，以确定在单导管水平内与浸润性乳腺癌相关的前体瘤的转录组和遗传变化。我们研究HER 2扩增导管原位癌（DCIS）作为一个事件，可以通过荧光原位杂交（FISH）和免疫组化固定石蜡包埋组织的定量和空间定位。通过将HER 2-FISH与激光捕获显微切割（LCM）Smart-3SEQ方法相结合，我们发现DCIS中的HER 2扩增改变了转录组学特征并增加了拷贝数变异（CNV）的多样性。特别地，干扰素信号传导途径在DCIS中被HER 2扩增激活，这可以在HER 2阳性乳腺癌中提供延长的干扰素信号传导激活。观察到具有不同CNV谱的HER 2扩增DCIS的多个亚克隆，表明在获得HER 2扩增时发生了多个事件。值得注意的是，DCIS在HER 2扩增之前获得关键的转录组学变化和CNV事件，这表明预扩增的DCIS可能会产生一种细胞状态，以获得HER 2扩增，从而获得生长优势。通过使用基因组的方法，是空间取向的，这项研究确定了几个功能，似乎产生洞察肿瘤进展癌前病变在一个单一的管道水平。在线版本包含补充材料，可通过10.1186/s13058-021-01451-6获得。
The acquisition of oncogenic drivers is a critical feature of cancer progression. For some carcinomas, it is clear that certain genetic drivers occur early in neoplasia and others late. Why these drivers are selected and how these changes alter the neoplasia’s fitness is less understood. Here we use spatially oriented genomic approaches to identify transcriptomic and genetic changes at the single-duct level within precursor neoplasia associated with invasive breast cancer. We study HER2 amplification in ductal carcinoma in situ (DCIS) as an event that can be both quantified and spatially located via fluorescence in situ hybridization (FISH) and immunohistochemistry on fixed paraffin-embedded tissue. By combining the HER2-FISH with the laser capture microdissection (LCM) Smart-3SEQ method, we found that HER2 amplification in DCIS alters the transcriptomic profiles and increases diversity of copy number variations (CNVs). Particularly, interferon signaling pathway is activated by HER2 amplification in DCIS, which may provide a prolonged interferon signaling activation in HER2-positive breast cancer. Multiple subclones of HER2-amplified DCIS with distinct CNV profiles are observed, suggesting that multiple events occurred for the acquisition of HER2 amplification. Notably, DCIS acquires key transcriptomic changes and CNV events prior to HER2 amplification, suggesting that pre-amplified DCIS may create a cellular state primed to gain HER2 amplification for growth advantage. By using genomic methods that are spatially oriented, this study identifies several features that appear to generate insights into neoplastic progression in precancer lesions at a single-duct level. The online version contains supplementary material available at 10.1186/s13058-021-01451-6.
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影响因子：
64.8
作者：
Nik-Zainal S;Davies H;Staaf J;Ramakrishna M;Glodzik D;Zou X;Martincorena I;Alexandrov LB;Martin S;Wedge DC;Van Loo P;Ju YS;Smid M;Brinkman AB;Morganella S;Aure MR;Lingjærde OC;Langerød A;Ringnér M;Ahn SM;Boyault S;Brock JE;Broeks A;Butler A;Desmedt C;Dirix L;Dronov S;Fatima A;Foekens JA;Gerstung M;Hooijer GK;Jang SJ;Jones DR;Kim HY;King TA;Krishnamurthy S;Lee HJ;Lee JY;Li Y;McLaren S;Menzies A;Mustonen V;O'Meara S;Pauporté I;Pivot X;Purdie CA;Raine K;Ramakrishnan K;Rodríguez-González FG;Romieu G;Sieuwerts AM;Simpson PT;Shepherd R;Stebbings L;Stefansson OA;Teague J;Tommasi S;Treilleux I;Van den Eynden GG;Vermeulen P;Vincent-Salomon A;Yates L;Caldas C;van't Veer L;Tutt A;Knappskog S;Tan BK;Jonkers J;Borg Å;Ueno NT;Sotiriou C;Viari A;Futreal PA;Campbell PJ;Span PN;Van Laere S;Lakhani SR;Eyfjord JE;Thompson AM;Birney E;Stunnenberg HG;van de Vijver MJ;Martens JW;Børresen-Dale AL;Richardson AL;Kong G;Thomas G;Stratton MR
通讯作者：
Stratton MR
DOI：
10.1080/01635581.2020.1801777
发表时间：
2020-08-06
影响因子：
2.9
作者：
Hu, Zhiqiang;Wang, Hui;Wang, Jing
通讯作者：
Wang, Jing
影响因子：
7
作者：
Foley, Joseph W.;Zhu, Chunfang;West, Robert B.
通讯作者：
West, Robert B.
影响因子：
7
作者：
Navin, Nicholas;Krasnitz, Alexander;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
64.5
作者：
Ciriello G;Gatza ML;Beck AH;Wilkerson MD;Rhie SK;Pastore A;Zhang H;McLellan M;Yau C;Kandoth C;Bowlby R;Shen H;Hayat S;Fieldhouse R;Lester SC;Tse GM;Factor RE;Collins LC;Allison KH;Chen YY;Jensen K;Johnson NB;Oesterreich S;Mills GB;Cherniack AD;Robertson G;Benz C;Sander C;Laird PW;Hoadley KA;King TA;TCGA Research Network;Perou CM
通讯作者：
Perou CM