Journal of Molecular Diagnostics最新文献_第10页

Sensitivity and Specificity of Chimerism Tests in Predicting Leukemia Relapse Using Increasing Mixed Chimerism 利用不断增加的混合嵌合体预测白血病复发的嵌合体检验灵敏度和特异性

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-11-25 DOI: 10.1016/j.jmoldx.2024.09.003

Ruoheng Zhang , Yimeng Shang , Joseph Cioccio , Kevin Rakszawski , Myles Nickolich , Christopher Ehmann , Yoshitaka Inoue , Seema Naik , Witold Rybka , Hong Zheng , Joseph Mierski , Brooke Silar , Jason Liao , Robert Greiner , Valerie Brown , David Claxton , Jing Ning , Shouhao Zhou , Shin Mineishi , Kentaro Minagawa , Hiroko Shike

{"title":"Sensitivity and Specificity of Chimerism Tests in Predicting Leukemia Relapse Using Increasing Mixed Chimerism","authors":"Ruoheng Zhang , Yimeng Shang , Joseph Cioccio , Kevin Rakszawski , Myles Nickolich , Christopher Ehmann , Yoshitaka Inoue , Seema Naik , Witold Rybka , Hong Zheng , Joseph Mierski , Brooke Silar , Jason Liao , Robert Greiner , Valerie Brown , David Claxton , Jing Ning , Shouhao Zhou , Shin Mineishi , Kentaro Minagawa , Hiroko Shike","doi":"10.1016/j.jmoldx.2024.09.003","DOIUrl":"10.1016/j.jmoldx.2024.09.003","url":null,"abstract":"<div><div>Chimerism test was evaluated to predict leukemia relapse. Increasing mixed chimerism (IMC), defined as recipient increase ≥0.1% in peripheral blood total cell chimerism, was used as a surrogate of disease activity. Combination of quantitative PCR and short-tandem repeat method was applied to achieve high assay sensitivity. Total of 184 patients received stem cell transplant for acute myeloid leukemia (N = 110), acute lymphocytic leukemia (N = 41), myelodysplastic syndrome (N = 30), and 2389 chimerism tests (median follow-up, 1054 days). Sixty-six patients relapsed, and 118 patients did not. Cumulative incidence of relapse increased after 1 IMC or ≥2 consecutive IMCs (hazard ratios, 9.9 and 44.4, respectively). Predicted percentage relapse by day 30 after IMC was 0% (0 IMC), 10% (1 IMC), and 40% (≥2 IMCs). The last chimerism results before relapse detected IMC in 57 of 66 relapsed patients (sensitivity, 86.4%). Nine patients had no IMC before relapse (false negative) because of rapidly evolving relapse (N = 4) or extramural relapse (N = 5). In 118 patients without relapse, 158 of 1873 tests detected IMC (false positive, 8.4%; specificity, 91.6%). The false-positive rates increased with higher percentage recipient T-cell chimerism levels, indicating T-cell contamination as a cause. Chimerism monitoring predicts relapse. However, caution must be taken for false-positive or false-negative IMCs. T-cell removal can improve chimerism test specificity in patients with mixed T-cell chimerism.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 12","pages":"Pages 1159-1170"},"PeriodicalIF":3.4,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Title page 扉页

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-11-01 DOI: 10.1016/S1525-1578(24)00230-7

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Disclosure Statement 披露声明

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-11-01 DOI: 10.1016/S1525-1578(24)00231-9

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Navigating the Flood 在洪水中航行：2019年冠状病毒疾病爆发期间的高效稿件处理。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-10-24 DOI: 10.1016/j.jmoldx.2024.03.011

Yi-Wei Tang , Barbara A. Zehnbauer

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25 Years of Publishing The Journal of Molecular Diagnostics 分子诊断学杂志》出版 25 周年。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-10-24 DOI: 10.1016/j.jmoldx.2024.08.003

Emily H. Essex

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The Era of Molecular Hematopathology 分子血液病理学时代：回到未来。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-10-24 DOI: 10.1016/j.jmoldx.2024.06.011

Pawel Mroz , Mark D. Ewalt , Susan E. Harley , Patricia C. Tsang , Rena R. Xian , Craig R. Soderquist

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Detection and Interpretation of Clonal Hematopoiesis Variants during Routine Solid Tumor Next-Generation Sequencing 常规实体瘤新一代测序过程中克隆造血变异的检测与解读：单个机构的经验。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-10-02 DOI: 10.1016/j.jmoldx.2024.09.004

Adil Menon, Madina Sukhanova, Kevin L. Nocito, Juehua Gao, Lawrence J. Jennings, Erica R. Vormittag-Nocito

{"title":"Detection and Interpretation of Clonal Hematopoiesis Variants during Routine Solid Tumor Next-Generation Sequencing","authors":"Adil Menon, Madina Sukhanova, Kevin L. Nocito, Juehua Gao, Lawrence J. Jennings, Erica R. Vormittag-Nocito","doi":"10.1016/j.jmoldx.2024.09.004","DOIUrl":"10.1016/j.jmoldx.2024.09.004","url":null,"abstract":"<div><div>Clonal hematopoiesis (CH) and clonal cytopenia of undetermined significance (CCUS) are recently recognized diagnostic entities that serve as independent risk factors for cardiovascular disease and myeloid malignancy. CH is an incidental finding, and evaluation of the incidence of CH/CCUS-associated mutations in solid tumor next-generation sequencing samples was undertaken to better understand the prevalence of mutations in this population. A retrospective review of clinical sequencing data for solid tumor malignancies diagnosed between February 2022 and April 2023 on next-generation sequencing data was performed. Cases were reviewed for variants in genes associated with CH/CCUS. Variant allele frequencies and other factors of the sequencing data were assessed for determining risk of CH/CCUS. A total of 2479 cases were evaluated during the study period. Of these, 29 cases demonstrated potential CH/CCUS-associated mutations, with a total of 33 variants identified. These were identified in a variety of tumor types, with gliomas being the most common. Significant cardiac histories were found in over half of cases identified, and few cases had abnormal blood counts. Detailed criteria for flagging variants as suspicious for CH and recommendations for these criteria as future guidelines for reporting are described. These variants are incidental findings that require more extensive follow-up or change in therapy management using a single institutional cohort.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 12","pages":"Pages 1149-1158"},"PeriodicalIF":3.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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A Single Multiplex PCR and Single-Nucleotide Extension Assay for the Detection of Common Thanatophoric Dysplasia I and II Mutations 用于检测常见甲状腺发育不良 I 型和 II 型突变的单一多重 PCR 和单核苷酸延伸测定。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-09-30 DOI: 10.1016/j.jmoldx.2024.08.008

Mohamed A. Jama , N. Scott Reading , Eric Fredrickson , Sherin Shaaban , Yuan Ji

{"title":"A Single Multiplex PCR and Single-Nucleotide Extension Assay for the Detection of Common Thanatophoric Dysplasia I and II Mutations","authors":"Mohamed A. Jama , N. Scott Reading , Eric Fredrickson , Sherin Shaaban , Yuan Ji","doi":"10.1016/j.jmoldx.2024.08.008","DOIUrl":"10.1016/j.jmoldx.2024.08.008","url":null,"abstract":"<div><div>Mutation analysis provides confirmation of a clinical and radiological diagnosis of thanatophoric dysplasia types I and II (TD I and II). We developed a single multiplexed PCR and a single-nucleotide extension (SNE) assay to identify 14 common mutations causing 99% of TD I and TD II, including the challenging three adjacent mutations in the stop codon of exon 18 of the <em>FGFR3</em> gene. The assay design also provides a solution for resolving SNE PCR product sizing using performance optimized polymer-7. The assay was validated using 37 previously characterized, de-identified patient samples representing the nine wild-types and 10 of 14 mutant genotypes. Four artificial templates were synthesized to mimic four TD I mutations not represented in the available patient samples. Fragment size and fluorophore channel for each SNE product from 10 samples and the four artificial templates were used to define bins and panels for analysis with GeneMarker version 3.0 and GeneMapper version 6.0 software. Allele calls (bin placement within the panels) were verified using the remaining 27 previously characterized samples. This TD I and II PCR and SNE assay is a robust multiplexed assay, streamlined, to identify 14 mutations in one single reaction. This assay has a shorter turnaround time in comparison to traditional Sanger or next-generation sequencing.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 12","pages":"Pages 1102-1108"},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interlaboratory Harmonization Study and Prospective Evaluation of the PURE–Trypanosoma cruzi–Loop-Mediated Isothermal Amplification Assay for Detecting Parasite DNA in Newborn's Dried Blood Spots 用于检测新生儿干血斑中寄生虫 DNA 的 PURE-T. cruzi-LAMP 分析法的实验室间协调研究和前瞻性评估。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-09-30 DOI: 10.1016/j.jmoldx.2024.08.007

Silvia A. Longhi , Lady J. García-Casares , Arturo Muñoz-Calderón , Lucía Irazu , Marcelo A. Rodríguez , Gustavo Landfried , Julio Alonso-Padilla , Alejandro G. Schijman , Chagas-Group

{"title":"Interlaboratory Harmonization Study and Prospective Evaluation of the PURE–Trypanosoma cruzi–Loop-Mediated Isothermal Amplification Assay for Detecting Parasite DNA in Newborn's Dried Blood Spots","authors":"Silvia A. Longhi , Lady J. García-Casares , Arturo Muñoz-Calderón , Lucía Irazu , Marcelo A. Rodríguez , Gustavo Landfried , Julio Alonso-Padilla , Alejandro G. Schijman , Chagas-Group","doi":"10.1016/j.jmoldx.2024.08.007","DOIUrl":"10.1016/j.jmoldx.2024.08.007","url":null,"abstract":"<div><div>Timely diagnosis of vertical <em>Trypanosoma cruzi</em> infections involves microscopy-based detection of circulating parasites from peripheral blood, which lacks sensitivity and is operator dependent. Consequently, most children born to <em>T. cruzi</em>–infected mothers are required to undergo serological testing after 9 months, which risks loss to follow-up. Alternatively, the loop-mediated isothermal amplification (LAMP) test for <em>T. cruzi</em> DNA offers high analytical and clinical performance and is easy to use in low-complexity laboratories. Recently, we optimized this technique using an ultrarapid DNA extraction method combined with the LAMP in dried blood spots (DBSs) on Flinders Technology Associates cards. The procedure has been implemented in 10 public maternities across Paraguay, Bolivia, and Argentina, involving the training of 14 technicians. Operators' performance was evaluated using a standardized DBS testing panel for harmonization, including negative controls and DBS samples artificially contaminated with <em>T. cruzi</em> at 50 and 20 cells/mL. There was strong agreement (ĸ = 0.924) for controls and 50 cells/mL samples, and good agreement (ĸ = 0.718) across all testing panels, even at the detection limit of the test. A prospective study collected 306 DBSs from 222 newborns at birth and/or 2 months, detecting <em>T. cruzi</em> microscopically in four cases. LAMP identified eight positive cases and perfectly aligned with real-time PCR (ĸ = 1), demonstrating higher sensitivity than microscopic observation for early detection of infection in infants.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 12","pages":"Pages 1055-1064"},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High Prevalence of Chromosomal Rearrangements and LINE Retrotranspositions Detected in Formalin-Fixed, Paraffin-Embedded Colorectal Cancer Tissue 在福尔马林固定石蜡包埋的结直肠癌组织中检测到高流行率的染色体重排和 LINE 逆转。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-09-26 DOI: 10.1016/j.jmoldx.2024.08.004

Carmen Rubio-Alarcón , Ellen Stelloo , Daan C.L. Vessies , Iris van 't Erve , Nienke J. Mekkes , Joost Swennenhuis , Soufyan Lakbir , Elisabeth J. van Bree , Marianne Tijssen , Pien Delis-van Diemen , Mirthe Lanfermeijer , Theodora Linders , Daan van den Broek , Cornelis J.A. Punt , Jaap Heringa , Gerrit A. Meijer , Sanne Abeln , Harma Feitsma , Remond J.A. Fijneman

{"title":"High Prevalence of Chromosomal Rearrangements and LINE Retrotranspositions Detected in Formalin-Fixed, Paraffin-Embedded Colorectal Cancer Tissue","authors":"Carmen Rubio-Alarcón , Ellen Stelloo , Daan C.L. Vessies , Iris van 't Erve , Nienke J. Mekkes , Joost Swennenhuis , Soufyan Lakbir , Elisabeth J. van Bree , Marianne Tijssen , Pien Delis-van Diemen , Mirthe Lanfermeijer , Theodora Linders , Daan van den Broek , Cornelis J.A. Punt , Jaap Heringa , Gerrit A. Meijer , Sanne Abeln , Harma Feitsma , Remond J.A. Fijneman","doi":"10.1016/j.jmoldx.2024.08.004","DOIUrl":"10.1016/j.jmoldx.2024.08.004","url":null,"abstract":"<div><div>Structural variants (SVs) caused by chromosomal rearrangements in common fragile sites or long interspersed nuclear element (LINE) retrotranspositions are highly prevalent in colorectal cancer. However, methodology for the targeted detection of these SVs is lacking. This article reports the use of formalin-fixed, paraffin-embedded targeted-locus capture (FFPE-TLC) sequencing as a novel technology for the targeted detection of tumor-specific SVs. Analysis of 29 FFPE colorectal tumor samples and 8 matched normal samples revealed tumor-specific SVs in 24 patients (83%), with a median of 2 SVs per patient (range, 1 to 21). A total of 104 SVs were found in the common fragile site–associated genes <em>MACROD2</em>, <em>PRKN</em>, <em>FHIT</em>, and <em>WWOX</em> in 18 patients (62%), and 39 SVs caused by three LINE transposable elements were found in 15 patients (52%). Tumor specificity of SVs was independently verified by droplet digital PCR of tumor tissue DNA, and their applicability as plasma circulating tumor DNA biomarkers was demonstrated. FFPE-TLC sequencing enabled the detection of tumor-specific SVs caused by chromosomal rearrangements and LINE retrotranspositions in FFPE tissue. Therefore, FFPE-TLC sequencing facilitates the investigation of the biological and clinical effects of SVs using FFPE material from (retrospective) cohorts of cancer patients and has potential clinical applicability in the detection of SV biomarkers in the routine molecular diagnostics setting.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 12","pages":"Pages 1065-1080"},"PeriodicalIF":3.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0