Tumor Touch Imprints as Source for Whole Genome Analysis of Neuroblastoma Tumors

Brunner, C; Brunner-Herglotz, Bettina; Ziegler, Andrea; Frech, Christian; Amann, Gabriele; Ladenstein, Ruth; Ambros, Inge M.; Ambros, Peter F.

doi:10.1371/journal.pone.0161369

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…Preparation and IF-staining of tumor touch imprints and bone marrow cytospin preparations. Touch imprints were prepared from fresh primary tumors of 4 stage M neuroblastoma patients as previously described 21 . Mononuclear cells were isolated from bone marrow aspirates of 3 stage M neuroblastoma patients by density gradient centrifugation and cytospinned as described 22 .…”

Section: Background and Summarymentioning

confidence: 99%

An annotated fluorescence image dataset for training nuclear segmentation methods

et al. 2020

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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, staining intensity, cell density and nuclei aggregations. Machine learning-based segmentation methods can overcome these challenges, however high quality expert-annotated images are required for training. Currently, the limited number of annotated fluorescence image datasets publicly available do not cover a broad range of tissues and preparations. We present a comprehensive, annotated dataset including tightly aggregated nuclei of multiple tissues for the training of machine learning-based nuclear segmentation algorithms. The proposed dataset covers sample preparation methods frequently used in quantitative immunofluorescence microscopy. We demonstrate the heterogeneity of the dataset with respect to multiple parameters such as magnification, modality, signal-to-noise ratio and diagnosis. Based on a suggested split into training and test sets and additional single-nuclei expert annotations, machine learning-based image segmentation methods can be trained and evaluated.

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Section: Background and Summarymentioning

confidence: 99%

An annotated fluorescence image dataset for training nuclear segmentation methods

et al. 2020

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“…In addition to these relatively large genomic aberrations, deletion aberrations of single genes, parts of genes or point mutations e.g., TERT , ALK , ATRX, and ARID1A , have recently been described as having unfavorable clinical outcomes and implications for clinical management ( Brunner et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Application of the FISH method and high-density SNP arrays to assess genetic changes in neuroblastoma—research by one institute

Winnicka,

Skowera,

Stelmach

et al. 2024

Acta Biochim. Pol.

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Neuroblastoma is the most common extracranial solid tumor in children. Amplification of the MYCN gene has been observed in approximately 20%–30% of tumors. It is strongly correlated with advanced-stage disease, rapid tumor progression, resistance to chemotherapy and poor outcomes independent of patient age and stage of advanced disease. MYCN amplification identifies high-risk patients. To assess neuroblastoma tumors with MYCN amplification we used paraffin-embedded tissue sections in 57 patients and intraoperative tumor imprints in 10 patients by fluorescence in situ hybridization (FISH). Positive results for MYCN amplification have been observed in twelve patients’ paraffin-embedded tissue sections and in three patients’ intraoperative tumor imprints, which represents 22.4% of all patients tested in the analysis. Fluorescence in situ hybridization is a highly sensitive and useful technique for detecting MYCN amplification on paraffin-embedded tissue sections of neuroblastoma tumors and intraoperative tumor imprints thus facilitating therapeutic decisions based on the presence or absence of this important biologic marker. The presence of structural changes, regardless of MYCN gene amplification status, influences the clinical behavior of neuroblastoma. High-Density SNP Arrays have emerged as the perfect tools for detecting these changes due to their exceptional accuracy, sensitivity and ability to analyze copy number and allele information. Consequently, they are proven to be highly valuable in the genomic diagnosis of immature neuroectodermal tumors.

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“… 16 These IFDs do not lead to an absence of protein, but rather result in a shorter protein product. In neuroblastoma, both ATRX MEDs and point mutations have been reported, and these aberrations are strongly associated with ALT development 5 , 6 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 . ATRX aberrations are also present in various other pediatric 25 , 31 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 and adult cancers.…”

Section: Introductionmentioning

confidence: 99%

“…16 These IFDs do not lead to an absence of protein, but rather result in a shorter protein product. In neuroblastoma, both ATRX MEDs and point mutations have been reported, and these aberrations are strongly associated with ALT development 5,6,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] . ATRX aberrations are also present in various other pediatric 25,31, and adult cancers.…”

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“…| MATERIAL S AND ME THODS2.1 | Data acquisition and analysisTo obtain all reported pediatric cancers with known genetic ATRX aberrations, we carried out a thorough search in several databases.The last search was undertaken on April 30, 2020 and all identified papers were manually assessed for patients with known genetic ATRX aberrations. Twenty-one tumors with ATRX deletions described by Brunner et al19 and Abbasi et al17 were reanalyzed for this study for breakpoints and deleted exons. From all identified papers with neuroblastoma patients with ATRX aberrations, we collected the specific genetic mutation and a selection of the tumor/ patient data (TableS1).…”

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Mutational spectrum of ATRX aberrations in neuroblastoma and associated patient and tumor characteristics

et al. 2022

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Neuroblastoma is the most common extracranial solid tumor in children. The chromatin remodeler ATRX is frequently mutated in high‐risk patients with a poor prognosis. Although many studies have reported ATRX aberrations and the associated clinical characteristics in neuroblastoma, a comprehensive overview is currently lacking. In this study, we extensively characterize the mutational spectrum of ATRX aberrations in neuroblastoma tumors reported in previous studies and present an overview of patient and tumor characteristics. We collected the data of a total of 127 neuroblastoma patients and three cell lines with ATRX aberrations originating from 20 papers. We subdivide the ATRX aberrations into nonsense, missense, and multiexon deletions (MEDs) and show that 68% of them are MEDs. Of these MEDs, 75% are predicted to be in‐frame. Furthermore, we identify a missense mutational hotspot region in the helicase domain. We also confirm that all three ATRX mutation types are more often identified in patients diagnosed at an older age, but still approximately 40% of the patients are aged 5 years or younger at diagnosis. Surprisingly, we found that 11q deletions are enriched in neuroblastomas with ATRX deletions compared to a reference cohort, but not in neuroblastomas with ATRX point mutations. Taken together, our data emphasizes a distinct ATRX mutation spectrum in neuroblastoma, which should be considered when studying molecular phenotypes and therapeutic strategies.

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Tumor Touch Imprints as Source for Whole Genome Analysis of Neuroblastoma Tumors

Cited by 6 publications

References 27 publications

An annotated fluorescence image dataset for training nuclear segmentation methods

An annotated fluorescence image dataset for training nuclear segmentation methods

Application of the FISH method and high-density SNP arrays to assess genetic changes in neuroblastoma—research by one institute

Mutational spectrum of ATRX aberrations in neuroblastoma and associated patient and tumor characteristics

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