Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.
Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.
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DOI：
10.1016/j.cell.2015.09.033
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发表时间：
2015-10-08
期刊：
影响因子：
64.5
通讯作者：
Perou CM
中科院分区：
文献类型：
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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
浸润性小叶癌（ILC）是浸润性乳腺癌中第二常见的组织学亚型。在这里，我们全面分析了817个乳腺肿瘤，包括127个ILC， 490个导管（IDC）和88个混合IDC/ILC。除了最著名的ILC遗传标志E-cadherin缺失外，我们还发现针对PTEN、TBX3和FOXA1的突变是ILC富集的特征。PTEN缺失与AKT磷酸化增加相关，在所有乳腺癌亚型中，ILC中磷酸化水平最高。空间聚集的FOXA1突变与FOXA1表达和活性的增加相关。相反，GATA3突变和高表达是Luminal A IDC的特征，表明在ILC和IDC中ER活性的不同调节。增殖和免疫相关特征决定了与生存差异相关的三种ILC转录亚型。混合IDC/ILC病例在分子上分为ILC样和IDC样，没有真正的杂交特征。这种多维分子图谱揭示了ILC的遗传基础，并提供了潜在的临床选择。
Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3 and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized Luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.