Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas.
Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas.
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DOI：
10.1186/s13058-022-01550-y
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发表时间：
2022-07-29
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--
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浸润性小叶乳腺癌（ILC）是第二常见的乳腺癌组织学亚型，与更常见的浸润性导管癌（IDC）相比，它具有独特的分子特征。虽然ILC和IDC的基因组和转录组学特征已经被表征，但ILC和IDC之间的全基因组染色质可及性模式差异在很大程度上仍未被探索。在这里，我们使用来自癌症基因组图谱（TCGA）乳腺癌转座酶可及染色质测序（ATAC-seq）数据集的原发性肿瘤，表征了ILC和IDC之间肿瘤固有染色质可及性的差异。我们确定了ILC和IDC中全基因组染色质可及性的不同模式。推断的患者特异性转录因子（TF）基序活性揭示了ILC和IDC肿瘤之间和内部的调节差异。ILC中EGR1、RUNX3、TP63、STAT6、SOX家族、TEAD家族TFs较高，IDC中ATF4、PBX3、SPDEF、PITX家族、FOX家族TFs较高。这项研究揭示了ILC和IDC不同的表观基因组特征，以及驱动癌症进展的活性tf，可能为患者预后提供有价值的信息。在线版本包含补充材料，可在10.1186/s13058-022-01550-y获得。
Invasive lobular breast carcinoma (ILC), the second most prevalent histological subtype of breast cancer, exhibits unique molecular features compared with the more common invasive ductal carcinoma (IDC). While genomic and transcriptomic features of ILC and IDC have been characterized, genome-wide chromatin accessibility pattern differences between ILC and IDC remain largely unexplored. Here, we characterized tumor-intrinsic chromatin accessibility differences between ILC and IDC using primary tumors from The Cancer Genome Atlas (TCGA) breast cancer assay for transposase-accessible chromatin with sequencing (ATAC-seq) dataset. We identified distinct patterns of genome-wide chromatin accessibility in ILC and IDC. Inferred patient-specific transcription factor (TF) motif activities revealed regulatory differences between and within ILC and IDC tumors. EGR1, RUNX3, TP63, STAT6, SOX family, and TEAD family TFs were higher in ILC, while ATF4, PBX3, SPDEF, PITX family, and FOX family TFs were higher in IDC. This study reveals the distinct epigenomic features of ILC and IDC and the active TFs driving cancer progression that may provide valuable information on patient prognosis. The online version contains supplementary material available at 10.1186/s13058-022-01550-y.
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影响因子：
45.3
作者：
CLARK, GM;OSBORNE, CK;MCGUIRE, WL
通讯作者：
MCGUIRE, WL
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
3.1
作者：
Chuan, Tian;Li, Tian;Yi, Cui
通讯作者：
Yi, Cui
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
影响因子：
50.3
作者：
Buchwalter G;Hickey MM;Cromer A;Selfors LM;Gunawardane RN;Frishman J;Jeselsohn R;Lim E;Chi D;Fu X;Schiff R;Brown M;Brugge JS
通讯作者：
Brugge JS