A5042836196- Fibroblast Growth Factor Research
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Animal Genetics and Reproduction
- Kruppel-like factors research
- Virus-based gene therapy research
- PI3K/AKT/mTOR signaling in cancer
- Eosinophilic Disorders and Syndromes
- Immune cells in cancer
- CAR-T cell therapy research
- Cytokine Signaling Pathways and Interactions
- Genomics and Chromatin Dynamics
- Breast Cancer Treatment Studies
- Galectins and Cancer Biology
- Breast Lesions and Carcinomas
- Advanced biosensing and bioanalysis techniques
- Cancer-related Molecular Pathways
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Macrophage Migration Inhibitory Factor
- Cutaneous lymphoproliferative disorders research
- Microbial metabolism and enzyme function
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
The Netherlands Cancer Institute
2011-2023
Cancer Research UK Manchester Institute
2023
University of Manchester
2023
Oncode Institute
2016-2022
Cancer Genomics Centre
2017
Vrije Universiteit Amsterdam
2010
Large-scale sequencing studies are rapidly identifying putative oncogenic mutations in human tumors. However, discrimination between passenger and driver events tumorigenesis remains challenging requires vivo validation reliable animal models of cancer. In this study, we describe a novel strategy for candidate tumor suppressors implicated invasive lobular breast carcinoma (ILC), which is hallmarked by loss the cell-cell adhesion molecule E-cadherin. We an approach to model ILC intraductal...
Abstract Somatic hotspot mutations and structural amplifications fusions that affect fibroblast growth factor receptor 2 (encoded by FGFR2 ) occur in multiple types of cancer 1 . However, clinical responses to FGFR inhibitors have remained variable 1–9 , emphasizing the need better understand which alterations are oncogenic therapeutically targetable. Here we apply transposon-based screening 10,11 tumour modelling mice 12,13 find truncation exon 18 (E18) Fgfr2 is a potent driver mutation....
In human cancers, FGFR signaling is frequently hyperactivated by deregulation of FGF ligands or activating mutations in the receptors such as gene amplifications, point mutations, and fusions. As such, inhibitors are considered an attractive therapeutic strategy for patients with family members. We previously identified Fgfr2 a key driver invasive lobular carcinoma (ILC) vivo insertional mutagenesis screen using Sleeping Beauty transposon system. Here we explore whether these FGFR-driven...
Retroviral and transposon-based insertional mutagenesis (IM) screens are widely used for cancer gene discovery in mice. Exploiting the full potential of IM requires methods high-throughput sequencing mapping transposon retroviral insertion sites. Current protocols based on ligation-mediated PCR amplification junction fragments from restriction endonuclease-digested genomic DNA, resulting biases due to uneven distribution enzyme recognition Consequently, sequence coverage cannot be assess...
Effective treatment of invasive lobular carcinoma (ILC) the breast is hampered by late detection, growth, distant metastasis, and poor response to chemotherapy. Phosphoinositide 3-kinase (PI3K) signaling, one major druggable oncogenic signaling networks, frequently activated in ILC. We investigated resistance AZD8055, an inhibitor mammalian target rapamycin (mTOR), K14-cre;Cdh1Flox/Flox;Trp53Flox/Flox (KEP) mouse model metastatic Inhibition mTOR blocked growth primary KEP tumors as well...
Insertional mutagenesis using engineered transposons is a potent forward genetic screening technique used to identify cancer genes in mouse model systems. In the analysis of these screens, transposon insertion sites are typically identified by targeted DNA-sequencing and subsequently assigned predicted target heuristics. As such, approaches provide no direct evidence that insertions actually affect their targets or how transcripts affected. To address this, we developed IM-Fusion, an...
Congenital disorders of glycosylation (CDG) are rare genetic with a spectrum clinical manifestations caused by abnormal N-glycosylation secreted and cell surface proteins. Over 130 genes implicated next generation sequencing further identifies potential disease drivers in affected individuals. However, functional testing these variants is challenging, making it difficult to distinguish pathogenic from non-pathogenic events. Using proximity labelling, we identified OST48 as protein that...
Abstract Invasive lobular carcinoma (ILC) is the second most common breast cancer subtype, accounting for 5% to 15% of tumors.The majority ILCs are characterized by complete loss cell adhesion protein E-cadherin encoded CDH1 gene. However, WAPcre;Cdh1F/F mice with mammary gland-specific do not develop ILC, unless coupled additional disruption a tumor suppressor gene, like Pten or Trp53. Compound mutant lesions that closely resemble human disease in terms histology and invasivity. genome-wide...
Abstract Invasive lobular carcinoma (ILC) accounts for 10-15% of breast cancer cases in women. One the characteristics this type is loss intercellular adhesion which facilitated by inactivating mutations E-cadherin. However E-cadherin alone not enough to induce ILC. An vivo Sleeping Beauty insertional mutagenesis screen was performed identify genes that together with contribute ILC development mice. In around 85% tumors were analyzed during one four hits observed, namely MYPT1, MYPT2, ASPP2...
<p>This file describes Supplementary experimental details regarding the cell viability, clonogenic and competition assays, preparation of membrane vesicles vesicular transport immunohistochemistry, immunoblotting, RNA sequencing analysis, amplification SB transposon insertions validation Fgfr2-Tbc1d1 fusion, Met qPCR copy number analysis statistical analysis.</p>
<p>Mutations (SNVs) identified for RTKs and genes involved in the MAPK-ERK signaling pathway donor, vehicle- AZD4547-treated tumors.</p>
<p>Overview of the sequenced tumor samples, including sample IDs, treatment information and type transplanted material.</p>
<p>Overview of insertions identified in the donor, vehicle- and AZD4547-treated tumors.</p>
<p>Supplementary Figures S1-5 show additional information regarding the Fgfr2-Tbc1d1 fusion, effect of AZD4547 on established WESB and WESB-Fgfr2 tumors tumor-derived cells, causes death observed with different treatment schedules, differential gene expression analysis multiple RTK family members overview insertions in genes across all used this study.</p>
<p>Mutations (SNVs) identified for RTKs and genes involved in the MAPK-ERK signaling pathway donor, vehicle- AZD4547-treated tumors.</p>
<p>Overview of the sequenced tumor samples, including sample IDs, treatment information and type transplanted material.</p>
<p>This file describes Supplementary experimental details regarding the cell viability, clonogenic and competition assays, preparation of membrane vesicles vesicular transport immunohistochemistry, immunoblotting, RNA sequencing analysis, amplification SB transposon insertions validation Fgfr2-Tbc1d1 fusion, Met qPCR copy number analysis statistical analysis.</p>
<p>Overview of insertions identified in the donor, vehicle- and AZD4547-treated tumors.</p>
<p>Supplementary Figures S1-5 show additional information regarding the Fgfr2-Tbc1d1 fusion, effect of AZD4547 on established WESB and WESB-Fgfr2 tumors tumor-derived cells, causes death observed with different treatment schedules, differential gene expression analysis multiple RTK family members overview insertions in genes across all used this study.</p>