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Open AccessIntegrative analysis of genomic amplification-dependent expression and loss-of-function screen identifies ASAP1 as a driver gene in triple-negative breast cancer progression
The genetically heterogeneous triple-negative breast cancer (TNBC) continues to be an intractable disease, due to lack of effective targeted therapies. Gene amplification is a major event in tumorigenesis. Gen...
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Article
Open AccessMulti-targeted kinase inhibition alleviates mTOR inhibitor resistance in triple-negative breast cancer
Owing to its genetic heterogeneity and acquired resistance, triple-negative breast cancer (TNBC) is not responsive to single-targeted therapy, causing disproportional cancer-related death worldwide. Combined t...
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Article
Open AccessAn increased cell cycle gene network determines MEK and Akt inhibitor double resistance in triple-negative breast cancer
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor clinical prognosis and limited targeted treatment strategies. Kinase inhibitor screening of a panel of 20 TNBC cell line...
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Article
Open AccessUncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes
Ttriple-negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype. Enhanced TNBC cell motility is a prerequisite of TNBC cell dissemination. Here, we apply an imaging-based RNA...
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Article
Open AccessA kinase inhibitor screen identifies a dual cdc7/CDK9 inhibitor to sensitise triple-negative breast cancer to EGFR-targeted therapy
The effective treatment of triple-negative breast cancer (TNBC) remains a profound clinical challenge. Despite frequent epidermal growth factor receptor (EGFR) overexpression and reliance on downstream signall...
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Article
Open AccessPartially methylated domains are hypervariable in breast cancer and fuel widespread CpG island hypermethylation
Global loss of DNA methylation and CpG island (CGI) hypermethylation are key epigenomic aberrations in cancer. Global loss manifests itself in partially methylated domains (PMDs) which extend up to megabases. ...
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Article
Open AccessCo-regulated gene expression of splicing factors as drivers of cancer progression
Splicing factors (SFs) act in dynamic macromolecular complexes to modulate RNA processing. To understand the complex role of SFs in cancer progression, we performed a systemic analysis of the co-regulation of ...
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Article
Author Correction: Landscape of somatic mutations in 560 breast cancer whole-genome sequences
In the Methods section of this Article, ‘greater than’ should have been ‘less than’ in the sentence ‘Putative regions of clustered rearrangements were identified as having an average inter-rearrangement distan...
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Article
Open AccessGene length corrected trimmed mean of M-values (GeTMM) processing of RNA-seq data performs similarly in intersample analyses while improving intrasample comparisons
Current normalization methods for RNA-sequencing data allow either for intersample comparison to identify differentially expressed (DE) genes or for intrasample comparison for the discovery and validation of g...
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Article
Open AccessT lymphocytes facilitate brain metastasis of breast cancer by inducing Guanylate-Binding Protein 1 expression
The discovery of genes and molecular pathways involved in the formation of brain metastasis would direct the development of therapeutic strategies to prevent this deadly complication of cancer. By comparing ge...
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Article
Open AccessConfirmation of a metastasis-specific microRNA signature in primary colon cancer
The identification of patients with high-risk stage II colon cancer who may benefit from adjuvant therapy may allow the clinical approach to be tailored for these patients based on an understanding of tumour b...
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Article
Open AccessPhosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer
In a previous study, we detected a significant association between phosphoserine aminotransferase 1 (PSAT1) hyper-methylation and mRNA levels to outcome to tamoxifen treatment in recurrent disease. We here aim...
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Article
Open AccessBreast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration
A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subty...
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Article
Open AccessPrognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients
We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an i...
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Article
Open AccessRecurrent HOXB13 mutations in the Dutch population do not associate with increased breast cancer risk
The HOXB13 p.G84E mutation has been firmly established as a prostate cancer susceptibility allele. Although HOXB13 also plays a role in breast tumor progression, the association of HOXB13 p.G84E with breast cance...
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Article
Landscape of somatic mutations in 560 breast cancer whole-genome sequences
We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93...
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Article
Open AccessAn 8-gene mRNA expression profile in circulating tumor cells predicts response to aromatase inhibitors in metastatic breast cancer patients
Molecular characterization of circulating tumor cells (CTC) is promising for personalized medicine. We aimed to identify a CTC gene expression profile predicting outcome to first-line aromatase inhibitors in m...
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Article
Open AccessUnderstanding drugs in breast cancer through drug sensitivity screening
With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breas...
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Article
Open AccessInt6 reduction activates stromal fibroblasts to enhance transforming activity in breast epithelial cells
The INT6 gene was first discovered as a site of integration in mouse mammary tumors by the mouse mammary tumor virus; however, INT6’s role in the development of human breast cancer remains largely unknown. By gen...
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Article
Open AccessDC-SCRIPT is a novel regulator of the tumor suppressor gene CDKN2B and induces cell cycle arrest in ERα-positive breast cancer cells
Breast cancer is one of the most common causes of cancer-related deaths in women. The estrogen receptor (ERα) is well known for having growth promoting effects in breast cancer. Recently, we have identified DC...
