| 1. |
- de Ståhl, Teresita Diaz, et al.
(författare)
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The Swedish childhood tumor biobank : systematic collection and molecular characterization of all pediatric CNS and other solid tumors in Sweden
- 2023
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Ingår i: Journal of Translational Medicine. - : BioMed Central (BMC). - 1479-5876. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Childhood Tumor Biobank (BTB) is a nonprofit national infrastructure for collecting tissue samples and genomic data from pediatric patients diagnosed with central nervous system (CNS) and other solid tumors. The BTB is built on a multidisciplinary network established to provide the scientific community with standardized biospecimens and genomic data, thereby improving knowledge of the biology, treatment and outcome of childhood tumors. As of 2022, over 1100 fresh-frozen tumor samples are available for researchers. We present the workflow of the BTB from sample collection and processing to the generation of genomic data and services offered. To determine the research and clinical utility of the data, we performed bioinformatics analyses on next-generation sequencing (NGS) data obtained from a subset of 82 brain tumors and patient blood-derived DNA combined with methylation profiling to enhance the diagnostic accuracy and identified germline and somatic alterations with potential biological or clinical significance. The BTB procedures for collection, processing, sequencing, and bioinformatics deliver high-quality data. We observed that the findings could impact patient management by confirming or clarifying the diagnosis in 79 of the 82 tumors and detecting known or likely driver mutations in 68 of 79 patients. In addition to revealing known mutations in a broad spectrum of genes implicated in pediatric cancer, we discovered numerous alterations that may represent novel driver events and specific tumor entities. In summary, these examples reveal the power of NGS to identify a wide number of actionable gene alterations. Making the power of NGS available in healthcare is a challenging task requiring the integration of the work of clinical specialists and cancer biologists; this approach requires a dedicated infrastructure, as exemplified here by the BTB.
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| 2. |
- Erickson, Andrew, et al.
(författare)
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The spatial landscape of clonal somatic mutations in benign and malignant tissue
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
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| 3. |
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| 4. |
- Kvastad, Linda, et al.
(författare)
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The spatial landscape of transcriptomes and genomes in pediatric brain tumors
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Treatment of pediatric brain tumors is continually being improved; still, there is a great need for new treatment options. Here we explore the spatial transcriptomic and genomic landscape in a cohort of pediatric brain tumors using a new generation of unbiased methodologies. We demonstrate the gene expression patterns of the essential cancer-related gene programs of epithelial-to-mesenchymal transition (EMT), the reverse process mesenchymal-to-epithelial transition (MET), and tumor microenvironment (TME) observations through microglia. Furthermore, we identify the gene expression of SPP1 by microglia in the TME as a potential prognostic mRNA marker - in pediatric brain tumor relapse patients.
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| 5. |
- Kvastad, Linda, et al.
(författare)
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The spatial RNA integrity number assay for in situ evaluation of transcriptome quality
- 2021
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- The RNA integrity number (RIN) is a frequently used quality metric to assess the completeness of rRNA, as a proxy for the corresponding mRNA in a tissue. Current methods operate at bulk resolution and provide a single average estimate for the whole sample. Spatial transcriptomics technologies have emerged and shown their value by placing gene expression into a tissue context, resulting in transcriptional information from all tissue regions. Thus, the ability to estimate RNA quality in situ has become of utmost importance to overcome the limitation with a bulk rRNA measurement. Here we show a new tool, the spatial RNA integrity number (sRIN) assay, to assess the rRNA completeness in a tissue wide manner at cellular resolution. We demonstrate the use of sRIN to identify spatial variation in tissue quality prior to more comprehensive spatial transcriptomics workflows. Kvastad et al. develop the spatial RNA Integrity Number (sRIN) assay that evaluates the RNA integrity at cellular resolution. This method improves the resolution of a similar method called the RNA Integrity Number (RIN), demonstrating spatial variation in the quality of RNA samples.
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| 6. |
- Pfeifer, Susan, et al.
(författare)
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Swedish Biobank for Childhood Tumors
- 2014
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Ingår i: Neuro-Oncology. - 1522-8517 .- 1523-5866. ; 16, s. 141-141
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Pfeifer, Susan, 1948-, et al.
(författare)
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The Swedish Pediatric Tumor Biobank
- 2014
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Ingår i: 16th International Symposium on Pediatric Neuro-Oncology in conjunction with the 8th St. Jude-VIVA Forum, 28 June - 2 July, 2014..
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Konferensbidrag (refereegranskat)
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