Inge Ambros

Inge Ambros
  • MD
  • Senior Researcher at Children's Cancer Research Institute

About

202
Publications
21,345
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9,129
Citations
Current institution
Children's Cancer Research Institute
Current position
  • Senior Researcher

Publications

Publications (202)
Article
Full-text available
In neuroblastoma, MYCN amplification and 11q-deletion are important, although incomplete, markers of high-risk disease. It is therefore relevant to characterize additional alterations that can function as prognostic and/or predictive markers. Using SNP-microarrays, a group of neuroblastoma patients showing amplification of one or multiple 12q loci...
Article
Introduction: Neuroblastoma is the most common solid tumor in infants and arises from progenitor cells during sympathoadrenal development. While the majority of primary tumor cells resembles adrenergic neurons, more undifferentiated mesenchymal or neural-crest cell-like phenotypes have been found, especially in pretreated and high-risk cases. In mo...
Preprint
Full-text available
The plastic potential of Schwann cells (SCs) is increasingly recognized to play a role after nerve injury and in diseases of the peripheral nervous system. In addition, reports on the interaction between SCs and immune cells indicate their involvement in inflammatory processes. However, data about the immunocompetence of human SCs are primarily der...
Article
Full-text available
Intratumour heterogeneity is a major cause of treatment failure in cancer. We present in-depth analyses combining transcriptomic and genomic profiling with ultra-deep targeted sequencing of multiregional biopsies in 10 patients with neuroblastoma, a devastating childhood tumour. We observe high spatial and temporal heterogeneity in somatic mutation...
Article
Full-text available
Purpose Neuroblastoma (NB) is the most frequent extracranial tumor in children. The detection of bone marrow (BM) involvement is crucial for correct staging and risk-adapted treatment. We compared three methods regarding the detection of NB involvement in BM. Methods Eighty-one patients with NB were included in this retrospective study. BM samples...
Article
Full-text available
While the bone marrow attracts tumor cells in many solid cancers leading to poor outcome in affected patients, comprehensive analyses of bone marrow metastases have not been performed on a single-cell level. We here set out to capture tumor heterogeneity and unravel microenvironmental changes in neuroblastoma, a solid cancer with bone marrow involv...
Article
Full-text available
Sequencing of cell-free DNA in the blood of cancer patients (liquid biopsy) provides attractive opportunities for early diagnosis, assessment of treatment response, and minimally invasive disease monitoring. To unlock liquid biopsy analysis for pediatric tumors with few genetic aberrations, we introduce an integrated genetic/epigenetic analysis met...
Article
Full-text available
Separating and labeling each nuclear instance (instance-aware segmentation) is the key challenge in nuclear image segmentation. Deep Convolutional Neural Networks have been demonstrated to solve nuclear image segmentation tasks across different imaging modalities, but a systematic comparison on complex immunofluorescence images has not been perform...
Article
Full-text available
Adult Schwann cells (SCs) possess an inherent plastic potential. This plasticity allows SCs to acquire repair-specific functions essential for peripheral nerve regeneration. Here, we investigate whether stromal SCs in benign-behaving peripheral neuroblastic tumors adopt a similar cellular state. We profile ganglioneuromas and neuroblastomas, rich a...
Article
Full-text available
We evaluated long-term outcome and genomic profiles in the Austrian Neuroblastoma Trial A-NB94 which applied a risk-adapted strategy of treatment (RAST) using stage, age and MYCN amplification (MNA) status for stratification. RAST ranged from surgery only to intensity-adjusted chemotherapy, single or multiple courses of high-dose chemotherapy (HDT)...
Preprint
Full-text available
Bone marrow commonly serves as a metastatic niche for disseminated tumor cells (DTCs) of solid cancers in patients with unfavorable clinical outcome. Single-cell assessment of bone marrow metastases is essential to decipher the entire spectrum of tumor heterogeneity in these cancers, however, has previously not been performed. Here we used multi-ep...
Article
Full-text available
Purpose: For localized, resectable neuroblastoma without MYCN amplification, surgery only is recommended even if incomplete. However, it is not known whether the genomic background of these tumors may influence outcome. Patients and methods: Diagnostic samples were obtained from 317 tumors, International Neuroblastoma Staging System stages 1/2A/...
Article
Full-text available
Fully-automated nuclear image segmentation is the prerequisite to ensure statistically significant, quantitative analyses of tissue preparations,applied in digital pathology or quantitative microscopy. The design of segmentation methods that work independently of the tissue type or preparation is complex, due to variations in nuclear morphology, st...
Article
Full-text available
Liquid biopsies as minimally invasive approach have the potential to revolutionize molecular diagnostics. Yet while protocols for sample handling and the isolation of circulating tumor DNA (ctDNA) are numerous, comprehensive guidelines for diagnostics and research considering all aspects of real-life multi-center clinical studies are currently not...
Preprint
Full-text available
The remarkable plasticity of Schwann cells (SCs) enables the acquisition of repair-specific functions essential for peripheral nerve regeneration. We hypothesized that this plastic potential is manifested in stromal SCs found within mostly benign-behaving peripheral neuroblastic tumors. To shed light on the cellular state and impact of stromal SCs,...
Preprint
Full-text available
Separating and labeling each instance of a nucleus (instance-aware segmentation) is the key challenge in segmenting single cell nuclei on fluorescence microscopy images. Deep Neural Networks can learn the implicit transformation of a nuclear image into a probability map indicating the class membership of each pixel (nucleus or background), but the...
Poster
Full-text available
Deep learning (DL) algorithms are achieving or even surpassing human-level performance in tasks like image classification or segmentation. Due to their fast development and exceptional performance, DL algorithms were introduced in various life science domains such as biomedical imaging, bioinformatics or computational biology. However, the outcome...
Article
Clinical decision-making in cancer and other diseases relies on timely and cost-effective genome-wide testing. Classical bioinformatic algorithms, such as Rawcopy, can support genomic analysis by calling genomic breakpoints and copy-number variations (CNVs), but often require manual data curation, which is error prone, time-consuming, and thus subs...
Article
Background: Poor prognosis and frequent relapses are major challenges for patients with high-risk neuroblastoma (NB), especially when tumors show amplification. High-dose chemotherapy triggers apoptosis, necrosis, and senescence, a cellular stress response leading to permanent proliferative arrest and a typical senescence-associated secretome (SASP...
Article
Neuroblastoma (NB) is the most common tumor diagnosed in the first year of life. More than 90% of stage M NB patients present with disseminated tumor cells (DTCs) in the bone marrow (BM). Although these cells represent a major obstacle to treatment, their global gene expression has, so far, been only poorly analyzed. GD2POS DTCs of stage M NB patie...
Preprint
Full-text available
Presented at WCB - Joint ICML and IJCAI 2018 Workshop on Computational Biology Diagnosis and risk stratification of cancer and many other diseases require the detection of genomic breakpoints as a prerequisite of calling copy number alterations (CNA). This, however, is still challenging and requires time-consuming manual curation. As deep-learning...
Preprint
Full-text available
Presented at WCB - Joint ICML and IJCAI 2018 Workshop on Computational Biology. Diagnosis and risk stratification of cancer and many other diseases require the detection of genomic breakpoints as a prerequisite of calling copy number alterations (CNA). This, however, is still challenging and requires time-consuming manual curation. As deep-learning...
Article
Full-text available
Background: In neuroblastoma (NB), the most powerful prognostic marker, the MYCN amplification (MNA), occasionally shows intratumoural heterogeneity (ITH), i.e. coexistence of MYCN-amplified and non-MYCN-amplified tumour cell clones, called heterogeneous MNA (hetMNA). Prognostication and therapy allocation are still unsolved issues. Methods: The...
Chapter
This chapter emphasizes detailed protocols for the effective establishment of highly enriched human Schwann cell cultures and their characterization via immunostaining. The Schwann cells are isolated from immediately dissociated fascicle tissue and expanded prior to purification. Two purification methods are described that use either fluorescence-a...
Article
Full-text available
Background: Neuroblastoma is characterized by substantial clinical heterogeneity. Despite intensive treatment, the survival rates of high-risk neuroblastoma patients are still disappointingly low. Somatic chromosomal copy number aberrations have been shown to be associated with patient outcome, particularly in low- and intermediate-risk neuroblasto...
Article
Neuroblastoma is the most common extracranial solid tumor in childhood. The vast majority of metastatic (M) stage patients present with disseminated tumor cells (DTCs) in the bone marrow (BM) at diagnosis and relapse. Although these cells represent a major obstacle in the treatment of neuroblastoma patients, insights into their expression profile r...
Article
Full-text available
Purpose: Tumor relapse is the most frequent cause of death in stage 4 neuroblastomas. Since genomic information on the relapse precursor cells could guide targeted therapy, our aim was to find the most appropriate tissue for identifying relapse-seeding clones. Experimental design: We analyzed 10 geographically and temporally separated samples of...
Article
Full-text available
Introduction Tumor touch imprints (TTIs) are routinely used for the molecular diagnosis of neuroblastomas by interphase fluorescence in-situ hybridization (I-FISH). However, in order to facilitate a comprehensive, up-to-date molecular diagnosis of neuroblastomas and to identify new markers to refine risk and therapy stratification methods, whole ge...
Data
Detailed SNP array and I-FISH results of neuroblastoma samples. This table lists segmental chromosomal aberrations typical for neuroblastomas (SCAs) and SCAs of so far unknown diagnostic relevance (atypical SCA), numerical chromosomal aberrations (NCAs), and aberrant copy numbers of single genes of selected chromosomes. Corresponding I-FISH results...
Data
SNP array and I-FISH results of non-neuroblastoma TTI samples. This table presents SCAs, NCAs, wc cnLOHs and altered single genes of possible interest in one Ewing tumor (ES01), one desmoplastic small round cell tumor (DSRCT01), one medulloblastoma (MB01) and one osteosarcoma (OS01). (XLSX)
Article
Full-text available
Intracranial classic (WHO grade II) and anaplastic (WHO grade III) ependymomas are among the most common tumors in pediatric patients and have due to frequent recurrences and late relapses a relatively poor outcome. The impact of histopathological grading on patient outcome is controversial and therefore, molecular prognostic and predictive markers...
Article
Full-text available
The remarkable feature of Schwann cells (SCs) to transform into a repair phenotype turned the spotlight on this powerful cell type. SCs provide the regenerative environment for axonal re-growth after peripheral nerve injury (PNI) and play a vital role in differentiation of neuroblastic tumors into a benign subtype of neuroblastoma, a tumor originat...
Conference Paper
MYCN-amplification and 11q-deletion are important, although incomplete, markers of high-risk neuroblastoma. Thus, characterization of additional genomic alterations that can be used as prognostic and/or predictive markers is of clinical importance in order to provide best treatment possible. By using SNP-microarrays we identified a small group of n...
Article
Purpose: For 60% of high risk neuroblastoma patients this tumor is still a deadly disease. Even though great progress has been achieved over the last decades concerning molecular classifiers and drug targets, most of the results are based on single biopsies of bulky tumors. However, recent data show that neuroblastoma tumors are frequently inhomoge...
Article
Full-text available
Amplification of MYCN is the signature genetic aberration of 20-25% of neuroblastoma and a stratifying marker associated with aggressive tumor behavior. The detection of heterogeneous MYCN amplification (hetMNA) poses a diagnostic dilemma due to the uncertainty of its relevance to tumor behavior. Here, we aimed to shed light on the genomic backgrou...
Article
Full-text available
Poor prognosis and frequent relapses are major challenges for patients with high-risk neuroblastoma (NB), especially when tumors show MYCN amplification. High-dose chemotherapy triggers apoptosis, necrosis and senescence, a cellular stress response leading to permanent proliferative arrest and a typical senescence-associated secretome (SASP). SASP...
Article
Neuroblastoma is a pediatric cancer of the sympathetic nervous system with wide heterogeneity regarding clinobiological subtypes, ranging from patients with tumors of spontaneous regression to patients with aggressive tumors with fatal outcome despite multimodal treatment. MYCN-amplification and 11q-deletion are important, although incomplete, mark...
Article
Intratumoral heterogeneous MYCN amplification (hetMNA) is an unusual event in neuroblastoma with unascertained biological and clinical implications. Diagnosis is based on the detection of MYCN amplification surrounded by non-amplified tumor cells by fluorescence in situ hybridization (FISH). To better define the genetic features of hetMNA tumors, w...
Data
Supplementary Figure 1 Tumor cell content before and after enrichment. Scatter plot shows the tumor cell content before and after enrichment for each sample. The five different groups (A–E) are shown in different colors and differently shaped symbols. Frozen samples were classified according to the tumor cell content (TCC) before enrichment: group...
Article
Full-text available
BACKGROUND:The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is assoc...
Article
Full-text available
Neuroblastoma is the most common extra-cranial solid tumor in childhood. Presence of disseminated tumor cells (DTCs) in the bone marrow (BM) at diagnosis and at relapse is a common event in stage M neuroblastomas. Although the clinical heterogeneity of disseminated neuroblastomas is frequently associated with genomic diversity, so far, only little...
Article
s: AACR Special Conference: Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; November 3-6, 2013; San Diego, CA Background: MYCN amplification (MNA) is the most powerful therapy-stratifying marker in neuroblastoma (NB). With recent technological advances and the analysis of different pieces of individual tumors it b...
Article
Full-text available
Neuroblastoma serves as a paradigm for applying tumor genomic data for determining patient prognosis and thus for treatment allocation. MYCN status, i.e., amplified vs. non-amplified, was one of the very first biomarkers in oncology to discriminate aggressive from less aggressive or even favorable clinical courses of neuroblastoma. However, MYCN am...
Article
Full-text available
Background: In the INRG dataset, the hypothesis that any segmental chromosomal alteration might be of prognostic impact in neuroblastoma without MYCN amplification (MNA) was tested. Methods: The presence of any segmental chromosomal alteration (chromosome 1p deletion, 11q deletion and/or chromosome 17q gain) defined a segmental genomic profile. On...
Article
Full-text available
In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse. In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES...
Data
Full-text available
Expression of myogenic and human sarcoma biomarker genes in murine MD mixed sarcomas. To study whether mixed sarcomas from MD-mice express select human sarcoma-related genes (rhabdomyosarcoma-marker genes: Myog, Myl4, Igf2, Prox1, a fibrosarcoma gene: Vcan, and liposarcoma-related genes: Pparg, Myo1e, Hoxa5, Plau), we subjected RNA isolated from pr...
Article
Full-text available
Albeit genetically highly heterogeneous, muscular dystrophies (MDs) share a convergent pathology leading to muscle wasting accompanied by proliferation of fibrous and fatty tissue, suggesting a common MD-pathomechanism. Here we show that mutations in muscular dystrophy genes (Dmd, Dysf, Capn3, Large) lead to the spontaneous formation of skeletal mu...
Article
Full-text available
Precise and comprehensive analysis of neuroblastoma genetics is essential for accurate risk evaluation and only pangenomic/multilocus approaches fulfill the present-day requirements. We present the establishment and validation of the PCR-based multiplex ligation-dependent probe amplification (MLPA) technique for neuroblastoma. A neuroblastoma-speci...
Article
Full-text available
Neuroblastoma serves as a paradigm for utilising tumour genomic data for determining patient prognosis and treatment allocation. However, before the establishment of the International Neuroblastoma Risk Group (INRG) Task Force in 2004, international consensus on markers, methodology, and data interpretation did not exist, compromising the reliabili...
Article
Background: Neuroblastoma serves as a paradigm for utilizing tumour genomic data for determining patient prognosis and treatment allocation. However, prior to the establishment of the International Neuroblastoma Risk Group (INRG) Task Force in 2004, international consensus on markers, methodology, and data interpretation did not exist, compromising...

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