Journal of Laboratory Medicine最新文献

{"title":"Novel GLDC variants causing nonketotic hyperglycinemia in Chinese patients","authors":"Xiang-you Zhao, Guoqing Zhang, S. Dong, R. Yao, Niu Li, Tingting Yu, F. Bei, Jian Wang","doi":"10.1515/labmed-2022-0089","DOIUrl":"https://doi.org/10.1515/labmed-2022-0089","url":null,"abstract":"Abstract Objectives Glycine decarboxylase gene (GLDC) mutations cause nonketotic hyperglycinemia (NKH). Patients of NKH usually have heterogeneous phenotypes including respiratory failure, lethargy, myoclonic jerks, and hypotonia. The excessive glycine accumulation in brain is a crucial pathogenic mechanism. Methods We performed a clinical phenotypic analysis of two Chinese patients and conducted whole exome sequencing to detect possible pathogenic genes. Transcriptional experiments were carried out to evaluate the impact of GLDC c.862-2A>G on GLDC transcript splicing. Results GLDC variants were identified in both patients who mainly presented with hypotonia, apnea, and lethargy patient 1 had compound heterozygous variants, which were c.334+5G>C and c.862-2A>G, while patient 2 had c.862-2A>G and c.2098C>G (p.P700A) in GLDC. Transcriptional experiments of GLDC c.862-2A>G revealed the presence of aberrant transcripts leading to truncated protein products. Conclusions Both patients were diagnosed with neonatal NKH. Two novel splice-site variations in GLDC, c.334+5G>C and c.862-2A>G, were identified. The c.862-2A>G variation was found in both patients and was confirmed to affect the splicing of GLDC. Our study enriched our knowledge of the genotypic and the phenotypic spectrum of NKH.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":"46 1","pages":"369 - 375"},"PeriodicalIF":1.2,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43639400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated assessment of immunofixations with deep neural networks","authors":"Christian Thiemann, Britta Klitzke, Philipp Martinetz, Philipp Grüning, Thomas Käster, E. Barth, Jan Kramer, T. Martinetz","doi":"10.1515/labmed-2022-0078","DOIUrl":"https://doi.org/10.1515/labmed-2022-0078","url":null,"abstract":"Abstract Objectives The reliable evaluation of immunofixation electrophoresis is part of the laboratory diagnosis of multiple myeloma. Until now, this has been done routinely by the subjective assessment of a qualified laboratory staff member. The possibility of subjective errors and relatively high costs with long staff retention are the challenges of this approach commonly used today. Methods Deep Convolutional Neural Networks are applied to the assessment of immunofixation images. In addition to standard monoclonal gammopathies (IgA-Kappa, IgA-Lambda, IgG-Kappa, IgG-Lambda, IgM-Kappa, and IgM-Lambda), also bi- or oligoclonal gammopathies, free chain gammopathies, non-pathological cases, and cases with no clear finding are detected. The assignment to one of these 10 classes comes with a confidence value. Results On a test data set with over 4,000 images, approximately 25% of the cases are sorted out as inconclusive or due to low confidence for subsequent manual evaluation. On the remaining 75%, about 3,000 cases, not even one is classified as falsely positive, and only one as falsely negative. The remaining few deviations of the automated assessment from the classifications assigned manually by experts are borderline cases or can be explained otherwise. As a software running on a standard desktop computer, the Deep Convolutional Neural Network needs less than a second for the assessment of an immunofixation image. Conclusions Assisting the laboratory expert in the assessment of immunofixation images can be a useful addition to laboratory diagnostics. However, the decision-making authority should always remain with the physician responsible for the findings.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":"46 1","pages":"331 - 336"},"PeriodicalIF":1.2,"publicationDate":"2022-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47448440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The DKTK EXLIQUID consortium – exploiting liquid biopsies to advance cancer precision medicine for molecular tumor board patients","authors":"Matthias Mack, Julian Broche, Stephen George, Zahra Hajjari, F. Janke, Lavanya Ranganathan, Mohammadreza Ashouri, S. Bleul, A. Desuki, Cecilia Engels, S. Fliedner, N. Hartmann, M. Hummel, M. Janning, Alexander Kiel, T. Köhler, Sebastian E. Koschade, M. Lablans, M. Lambarki, S. Loges, S. Lueong, S. Meyer, S. Ossowski, F. Scherer, C. Schroeder, P. Skowronek, C. Thiede, B. Uhl, J. Vehreschild, N. von Bubnoff, Sebastian A. Wagner, Tamara V. Werner, C. Westphalen, P. Fresser, H. Sültmann, I. Tinhofer, C. Winter","doi":"10.1515/labmed-2022-0071","DOIUrl":"https://doi.org/10.1515/labmed-2022-0071","url":null,"abstract":"Abstract Testing for genetic alterations in tumor tissue allows clinicians to identify patients who most likely will benefit from molecular targeted treatment. EXLIQUID – exploiting liquid biopsies to advance cancer precision medicine – investigates the potential of additional non-invasive tools for guiding therapy decisions and monitoring of advanced cancer patients. The term “liquid biopsy” (LB) refers to non-invasive analysis of tumor-derived circulating material such as cell-free DNA in blood samples from cancer patients. Although recent technological advances allow sensitive and specific detection of LB biomarkers, only few LB assays have entered clinical routine to date. EXLIQUID is a German Cancer Consortium (DKTK)-wide joint funding project that aims at establishing LBs as a minimally-invasive tool to analyze molecular changes in circulating tumor DNA (ctDNA). Here, we present the structure, clinical aim, and methodical approach of the new DKTK EXLIQUID consortium. Within EXLIQUID, we will set up a multicenter repository of high-quality LB samples from patients participating in DKTK MASTER and local molecular tumor boards, which use molecular profiles of tumor tissues to guide targeted therapies. We will develop LB assays for monitoring of therapy efficacy by the analysis of tumor mutant variants and tumor-specific DNA methylation patterns in ctDNA from these patients. By bringing together LB experts from all DKTK partner sites and exploiting the diversity of their particular expertise, complementary skills and technologies, the EXLIQUID consortium addresses the challenges of translating LBs into the clinic. The DKTK structure provides EXLIQUID a unique position for the identification of liquid biomarkers even in less common tumor types, thereby extending the group of patients benefitting from non-invasive LB testing. Besides its scientific aims, EXLIQUID is building a valuable precision oncology cohort and LB platform which will be available for future collaborative research studies within the DKTK and beyond.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":"46 1","pages":"321 - 330"},"PeriodicalIF":1.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43499520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal hematopoiesis of indeterminate potential: clinical relevance of an incidental finding in liquid profiling","authors":"G. Hoermann","doi":"10.1515/labmed-2022-0050","DOIUrl":"https://doi.org/10.1515/labmed-2022-0050","url":null,"abstract":"Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is a hematologic precursor lesion that is defined by the presence of somatic mutations in peripheral blood cells but without evidence for the presence of leukemia or another hematologic neoplasm. CHIP is frequent in elderly individuals and can be detected as incidental finding in liquid profiling of cell-free DNA. While liquid profiling assays aim to reduce the biological noise generated by CHIP and to discriminate solid cancer-associated from CHIP-associated mutation profiles, the finding of CHIP is of potential clinical relevance at its own. Overall, CHIP is associated with a moderate risk of progression to an overt hematologic neoplasm of 1% per year. The risk increases substantially in patients with unexplained blood count abnormalities, multiple mutations, or specific patterns of mutations. In patients with solid cancer, the presence of CHIP increases the risk for development of treatment-related myeloid neoplasms. In addition, CHIP has been associated with a number of non-hematological diseases and represents a previously unrecognized major risk factor for cardiovascular disease. The management of individuals diagnosed with CHIP includes both hematologic and cardiovascular risk assessment in a multidisciplinary setting. Additional evidence from interventional studies is needed to integrate CHIP into a personalized treatment approach for patients with solid cancer.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":"46 1","pages":"301 - 310"},"PeriodicalIF":1.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44758246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-invasive prenatal screening tests – update 2022","authors":"Elena Kypri, M. Ioannides, A. Achilleos, G. Koumbaris, P. Patsalis, M. Stumm","doi":"10.1515/labmed-2022-0023","DOIUrl":"https://doi.org/10.1515/labmed-2022-0023","url":null,"abstract":"Abstract Since 2012, non-invasive prenatal testing (NIPT) using cell-free DNA from maternal plasma is applied all over the world as highly efficient first-line or contingent screening approach for trisomy 13, 18 and 21. With further technical development the screening has expanded to other genetic conditions such as sex chromosome anomalies (SCAs), rare autosomal trisomies (RATs), microdeletions/microduplications, structural chromosomal aberrations and monogenic diseases. Meanwhile, commercial providers are offering a number of different tests, with variable performance, the application of which needs to be carefully evaluated to apply to the true needs of clinical practice. In our review we present the different NIPT methodologies and discuss the main strengths and limitations in the context of providing a responsible pregnancy management.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":"46 1","pages":"311 - 320"},"PeriodicalIF":1.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48521245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling disease and tissue-specific epigenetic signatures in cell-free DNA","authors":"Angela Oberhofer, A. Bronkhorst, Vida Ungerer, S. Holdenrieder","doi":"10.1515/labmed-2022-0031","DOIUrl":"https://doi.org/10.1515/labmed-2022-0031","url":null,"abstract":"Abstract Programmed cell death, accidental cell degradation and active extrusion constantly lead to the release of DNA fragments into human body fluids from virtually all cell and tissue types. It is widely accepted that these cell-free DNA (cfDNA) molecules retain the cell-type specific genetic and epigenetic features. Particularly, cfDNA in plasma or serum has been utilized for molecular diagnostics. The current clinically implemented liquid biopsy approaches are mostly based on detecting genetic differences in cfDNA molecules from healthy and diseased cells. Their diagnostic potential is limited to pathologies involving genetic alterations, by the low proportion of cfDNA molecules carrying the mutation(s) relative to the total cfDNA pool, and by the detection limit of employed techniques. Recently, research efforts turned to epigenetic features of cfDNA molecules and found that the tissue-of-origin of individual cfDNA molecules can be inferred from epigenetic characteristics. Analysis of, e.g., methylation patterns, nucleosome or transcription factor binding site occupancies, fragment size distribution or fragment end motifs, and histone modifications determined the cell or tissue-of-origin of individual cfDNA molecules. With this tissue-of origin-analysis, it is possible to estimate the contributions of different tissues to the total cfDNA pool in body fluids and find tissues with increased cell death (pathologic condition), expanding the portfolio of liquid biopsies beyond genetics and towards a wide range of pathologies, such as autoimmune disorders, cardiovascular diseases, and inflammation, among many others. In this review, we give an overview on the status of tissue-of-origin approaches and focus on what is needed to exploit the full potential of liquid biopsies towards minimally invasive screening methods with broad clinical applications.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":"46 1","pages":"283 - 294"},"PeriodicalIF":1.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49094614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid profiling – circulating nucleic acid diagnostics gains momentum","authors":"S. Holdenrieder, H. Klein, C. Winter","doi":"10.1515/labmed-2022-0096","DOIUrl":"https://doi.org/10.1515/labmed-2022-0096","url":null,"abstract":"","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":"46 1","pages":"203 - 205"},"PeriodicalIF":1.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42627621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating cell-free DNA and its clinical utility in cancer","authors":"Amanda Salviano-Silva, C. Maire, K. Lamszus, F. Ricklefs","doi":"10.1515/labmed-2022-0047","DOIUrl":"https://doi.org/10.1515/labmed-2022-0047","url":null,"abstract":"Abstract Liquid biopsies are a valuable non-invasive biomarker source for the diagnosis, prognosis and monitoring of cancer patients. The detection of circulating cell-free DNA (cfDNA) derived from tumor cells (ctDNA) has emerged as a promising clinical approach, as their levels are elevated in many cancers and contains tumor-related mutations and specific methylation patterns. ctDNA can be released from tumor cells into the bloodstream, either linked to extracellular vesicles (EV-DNA) or in an EV-free form when associated with nucleosomes and other proteins, or even as a component of macromolecular structures such as neutrophil extracellular traps (NET DNA). These different types of cfDNA can mirror cancer progression and predict patient outcome. This review presents the recent benefits of cfDNA in cancer, distinguishing between EV-DNA and EV-free DNA, and highlights their clinical utility.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":"46 1","pages":"265 - 272"},"PeriodicalIF":1.2,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44492565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer screening by circulating tumor DNA (ctDNA) – recent breakthroughs and chronic pitfalls","authors":"S. Holdenrieder, Vida Ungerer, Angela Oberhofer, A. Bronkhorst","doi":"10.1515/labmed-2022-0029","DOIUrl":"https://doi.org/10.1515/labmed-2022-0029","url":null,"abstract":"Abstract Early detection is crucial for optimal treatment and prognosis of cancer. New approaches for pan-cancer screening comprise the comprehensive characterization of circulating tumor DNA (ctDNA) in plasma by next generation sequencing and molecular profiling of mutations and methylation patterns, as well as fragmentation analysis. These promise the accurate detection and localization of multiple cancers in early disease stages. However, studies with real screening populations have to show their clinical utility and practicability.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":"46 1","pages":"247 - 253"},"PeriodicalIF":1.2,"publicationDate":"2022-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41854124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are extracellular vesicles ready for the clinical laboratory?","authors":"D. Enderle, M. Noerholm","doi":"10.1515/labmed-2022-0064","DOIUrl":"https://doi.org/10.1515/labmed-2022-0064","url":null,"abstract":"Abstract The diagnostic potential of exosomes and extracellular vesicles (EVs) for liquid biopsies was first demonstrated over a decade ago, but despite a lot of progress in the scientific field there are still very few applications of EVs that are ready for implementation in clinical laboratories for routine diagnostic use. Despite good options for routine isolation of EVs and a wide analyte target space for assay development (incl. RNA, DNA, proteins and intact EVs) assessable by standard detection technologies, the attrition rate in translating biomarker reports in the academic literature to clinical assays is very high. While there are examples of successful development, the largest obstacle to increased clinical utilization is the lack of good biomarkers that can withstand rigid clinical validation, and which make use of the EVs’ unique capabilities as a biomarker platform.","PeriodicalId":55986,"journal":{"name":"Journal of Laboratory Medicine","volume":"46 1","pages":"273 - 282"},"PeriodicalIF":1.2,"publicationDate":"2022-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41355358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}