Erratum to: Genome co-amplification upregulates a mitotic gene network activity that predicts outcome and response to mitotic protein inhibitors in breast cancer
| العنوان: | Erratum to: Genome co-amplification upregulates a mitotic gene network activity that predicts outcome and response to mitotic protein inhibitors in breast cancer |
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| المؤلفون: | Sylvie Laquerre, Carlos Caldas, Richard Wooster, James E. Korkola, Jeff Jackson, Marc E. Lenburg, Shenda Gu, Mary Ann Hardwicke, Samuel Aparicio, Joe W. Gray, Laura M. Heiser, Shamith A. Samarajiwa, Barbara L. Weber, Jose A. Seoane, Zhi Hu, Amanda Esch, Kenneth Wood, Jian-Hua Mao, Ge Huang, Nicholas J. Wang, Christina Curtis, Heidi S. Feiler, Paul T. Spellman, Nora Bayani, Mark A. Dane |
| المصدر: | Breast cancer research : BCR, vol 19, iss 1 Breast Cancer Research : BCR |
| بيانات النشر: | eScholarship, University of California, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Medicine(all), computer.internet_protocol, Oncology and Carcinogenesis, Gene regulatory network, Novel therapeutics, Biology, Bioinformatics, medicine.disease, Genome, Given name, Predictive biomarker, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, Mitotic index, Oncology & Carcinogenesis, computer, Mitosis, XML, Research Article |
| الوصف: | Background High mitotic activity is associated with the genesis and progression of many cancers. Small molecule inhibitors of mitotic apparatus proteins are now being developed and evaluated clinically as anticancer agents. With clinical trials of several of these experimental compounds underway, it is important to understand the molecular mechanisms that determine high mitotic activity, identify tumor subtypes that carry molecular aberrations that confer high mitotic activity, and to develop molecular markers that distinguish which tumors will be most responsive to mitotic apparatus inhibitors. Methods We identified a coordinately regulated mitotic apparatus network by analyzing gene expression profiles for 53 malignant and non-malignant human breast cancer cell lines and two separate primary breast tumor datasets. We defined the mitotic network activity index (MNAI) as the sum of the transcriptional levels of the 54 coordinately regulated mitotic apparatus genes. The effect of those genes on cell growth was evaluated by small interfering RNA (siRNA). Results High MNAI was enriched in basal-like breast tumors and was associated with reduced survival duration and preferential sensitivity to inhibitors of the mitotic apparatus proteins, polo-like kinase, centromere associated protein E and aurora kinase designated GSK462364, GSK923295 and GSK1070916, respectively. Co-amplification of regions of chromosomes 8q24, 10p15-p12, 12p13, and 17q24-q25 was associated with the transcriptional upregulation of this network of 54 mitotic apparatus genes, and we identify transcription factors that localize to these regions and putatively regulate mitotic activity. Knockdown of the mitotic network by siRNA identified 22 genes that might be considered as additional therapeutic targets for this clinically relevant patient subgroup. Conclusions We define a molecular signature which may guide therapeutic approaches for tumors with high mitotic network activity. Electronic supplementary material The online version of this article (doi:10.1186/s13058-016-0728-y) contains supplementary material, which is available to authorized users. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5221d75b2ce700b90775bcd8c90ec62e https://escholarship.org/uc/item/2jj2x97s |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5221d75b2ce700b90775bcd8c90ec62e |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |