Journal of Molecular Diagnostics最新文献

Twenty-Five Years of Germline Genetic Testing and What May Lie Ahead 25 年来的种系遗传检测及未来展望

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-11-25 DOI: 10.1016/j.jmoldx.2024.06.013

Victoria M. Pratt , Sara Akhavanfard , Jane Houldsworth , Jennifer J. Laffin , Ann M. Moyer , Honey V. Reddi , Stuart A. Scott , Matthew S. Lebo

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A New Serotyping Method of Streptococcus pneumoniae Based on CRISPR/Cas9–Targeted Sequencing 基于 CRISPR/Cas9 靶向测序的肺炎链球菌血清分型新方法

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-11-25 DOI: 10.1016/j.jmoldx.2024.08.009

Yustinus Maladan , Endah Retnaningrum , Budi Setiadi Daryono , Rosantia Sarassari , Ratna Fathma Sari , Sarah Azhari Balqis , Ghina Athyah Wahid , Dodi Safari

{"title":"A New Serotyping Method of Streptococcus pneumoniae Based on CRISPR/Cas9–Targeted Sequencing","authors":"Yustinus Maladan , Endah Retnaningrum , Budi Setiadi Daryono , Rosantia Sarassari , Ratna Fathma Sari , Sarah Azhari Balqis , Ghina Athyah Wahid , Dodi Safari","doi":"10.1016/j.jmoldx.2024.08.009","DOIUrl":"10.1016/j.jmoldx.2024.08.009","url":null,"abstract":"<div><div>Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) application for targeted sequencing has made a breakthrough in the genomic research era. High diversity in the capsular polysaccharide (<em>cps</em>) locus of <em>Streptococcus pneumoniae</em> has hampered identification of the serotype. This study developed a new serotyping method for <em>S. pneumoniae</em> using CRISPR/Cas9–targeted sequencing with the Oxford Nanopore Technologies platform. A probe was designed at the position of the <em>cps</em> locus using an excision approach on two sides flanking genes between the <em>dexB</em> and <em>aliA</em> genes with approximately 20 kb. A native barcoding method was used for multiplexing. The probe will attach to a specific side followed by attachment of CRISPR/Cas9 to cut the recognition area. The study used <em>de novo</em> assembly to reconstruct sequence reads, which were analyzed using PneumoCRISPR, a new serotyping pipeline for Oxford Nanopore Technologies sequencing data output. Four CRISPR/Cas9 probes have been designed and recognize the <em>cps</em> locus of <em>S. pneumoniae</em>. Serotyping results align precisely with serotyping data from whole-genome sequencing. This serotyping method also allows researchers to use multiple samples in a single run. The new serotyping method based on CRISPR/Cas9–targeted sequencing holds immense promise for serotype identification of <em>S. pneumoniae</em>.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 12","pages":"Pages 1045-1054"},"PeriodicalIF":3.4,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721844","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

Changes and Challenges in Molecular Diagnostics 分子诊断的变化与挑战

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-11-25 DOI: 10.1016/j.jmoldx.2024.06.012

Karen L. Kaul , Timothy J. O'Leary , Barbara Zehnbauer

引用次数: 0

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}

引用次数: 0

A CLIA/CAP Compliant Noninvasive Laboratory Developed Test for Early Detection of Pancreatic Ductal Adenocarcinoma. 符合 CLIA/CAP 标准的无创实验室开发的胰腺导管腺癌早期检测试剂盒。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-11-07 DOI: 10.1016/j.jmoldx.2024.10.001

Jian Tajbakhsh, Silvana Debernardi, Oleg Blyuss, Jianhao Bai, Ruifen Weng, Simon Lo, Stephen J Pandol, Tatjana Crnogorac-Jurcevic, Nirdesh K Gupta

{"title":"A CLIA/CAP Compliant Noninvasive Laboratory Developed Test for Early Detection of Pancreatic Ductal Adenocarcinoma.","authors":"Jian Tajbakhsh, Silvana Debernardi, Oleg Blyuss, Jianhao Bai, Ruifen Weng, Simon Lo, Stephen J Pandol, Tatjana Crnogorac-Jurcevic, Nirdesh K Gupta","doi":"10.1016/j.jmoldx.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2024.10.001","url":null,"abstract":"<p><p>A noninvasive test for earlier detection of pancreatic cancer in individuals at higher risk is currently unavailable. To fill this void, we devised PancSure, a laboratory developed test in compliance with clinical regulations. PancSure is based on the protein biomarkers LYVE1 and REG1B, measured in urine by enzyme-linked immunosorbent assay, and commonly utilized serum/plasma CA19.9, with an updated version of the PancRISK algorithm for data interpretation. The test was validated in a cohort of 565 patients: 117 (21%) asymptomatic patients without any known pancreatic condition or malignancies, 242 (43%) symptomatic patients with benign pancreatic diseases and 206 (36%) confirmed cancers; 161 (77.5%) stages I-II and 45 (22.5%) stages III-IV. PancSure passed all specifications during analytical validation and distinguishes early-stage resectable cancer from asymptomatic individuals with AUC of 0.93 (0.89-0.97, 95% CI) and 85-90% sensitivity (SN) and 78-87% specificity (SP); from symptomatic patients with AUC of 0.86 (0.81-0.91, 95% CI) and 83-85% SN and 72-83% SP; and from all non-cancer patients (pooled controls) with AUC of 0.89 (0.84-0.93, 95% CI) and 83-85% SN and 78-87% SP. PancSure is a noninvasive clinical-grade test with a 48-hour turnover, ready for implementation without any costly instrumentation, thus providing a viable solution for the earlier detection of pancreatic cancer in at risk groups for improved patient care.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631478","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

Analysis of Molecular Testing for Suspected Myeloproliferative Neoplasm at a Hybrid Community-Academic Health System. 分析社区-学术混合医疗系统中疑似骨髓增生性肿瘤的分子检测。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-11-07 DOI: 10.1016/j.jmoldx.2024.10.003

Andrew B Stone, Ryan J Martinez, Cade Arries, Andrew C Nelson, Bharat Thyagarajan, Sophia Yohe, Pawel Mroz

{"title":"Analysis of Molecular Testing for Suspected Myeloproliferative Neoplasm at a Hybrid Community-Academic Health System.","authors":"Andrew B Stone, Ryan J Martinez, Cade Arries, Andrew C Nelson, Bharat Thyagarajan, Sophia Yohe, Pawel Mroz","doi":"10.1016/j.jmoldx.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2024.10.003","url":null,"abstract":"<p><p>Testing for somatic mutations in JAK2, MPL, and CALR genes is a crucial element in the diagnosis of myeloproliferative neoplasms (MPNs). This may have inadvertently led to increased requests for testing to rule out MPN, including clinical situations with low pretest probability. This article examines JAK2, MPL, and CALR testing by next-generation sequencing (NGS) with the goal of formulating practical guidelines to make test use more efficient and effective. NGS results from 1482 patients tested between 2015 and March 2022 were retrieved, along with corresponding bone marrow biopsies and complete blood cell count results performed within 90 days before NGS, and 245 cases (16.5%) were positive for pathogenic variants in JAK2, MPL, or CALR genes. The findings showed an increase in the proportion of positive cases with patient age, and a statistically significant difference in red blood cell counts and platelet counts among patients with positive versus negative results. Using these factors, simple algorithms were constructed to predict positive results with a maximum sensitivity of 91%, while potentially eliminating 28% of negative test results. However, these models still failed to identify approximately 9% of patients with MPNs. Among these missed patients, many had either primary myelofibrosis or myelodysplastic syndrome/MPN. Considering a simple triage model to help guide MPN testing could represent a more cost-effective approach, particularly if missed patients could be further reduced.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631496","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

Surveillance of Disease Progression in Metastatic Breast Cancer by Molecular Counting of Circulating Tumor DNA Using Plasma-SeqSensei Breast Cancer in Vitro Diagnostics Assay. 使用 Plasma-SeqSensei 乳腺癌体外诊断试剂盒对循环肿瘤 DNA 进行分子计数，监测转移性乳腺癌的病情进展。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-11-07 DOI: 10.1016/j.jmoldx.2024.08.011

Geert A Martens, Jan Demol, Franceska Dedeurwaerdere, Kristof De Smet, Janusz Wesolowski, Dieter De Smet

{"title":"Surveillance of Disease Progression in Metastatic Breast Cancer by Molecular Counting of Circulating Tumor DNA Using Plasma-SeqSensei Breast Cancer in Vitro Diagnostics Assay.","authors":"Geert A Martens, Jan Demol, Franceska Dedeurwaerdere, Kristof De Smet, Janusz Wesolowski, Dieter De Smet","doi":"10.1016/j.jmoldx.2024.08.011","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2024.08.011","url":null,"abstract":"<p><p>Circulating tumor DNA (ctDNA) quantification surpasses cancer antigen 15 to 3 for metastatic breast cancer surveillance. Clinical translation, however, is limited because of uncertainties about the optimal method and clinically valid ctDNA decision thresholds. Plasma-SeqSensei Breast Cancer IVD kit (PSS) is a novel assay for ctDNA molecular counting, detecting ≥0.06% variant allele fractions in AKT1, ERBB2, ESR1, KRAS, PIK3CA, and TP53. PSS was validated against droplet digital PCR (ddPCR) in 201 samples from 16 subjects with PIK3CA/TP53-mutated cancers, longitudinally sampled for a median of 93 (range, 18 to 113) weeks, three to five weekly. PSS and ddPCR ctDNA levels correlate significantly (Spearman ρ, 0.923; 95% CI, 0.898-0.941) across 0% to 43% variant allele frequency (VAF) range. PSS predicts 12-week progression with high clinical accuracy (area under the curve, 0.848; 95% CI, 0.790-0.894). PSS validates a previously developed ddPCR classifier: <10 copies/mL (0.25% VAF); excludes >100 copies/mL (2.5% VAF); and confirms progression, with negative predictive value (95% CI) of 83% (76%-88%) and positive predictive value (95% CI) of 91% (81%-96%) (weighted κ, 0.856; 95% CI, 0.797-0.915). PSS thus confirms robust clinical thresholds (10 to 100 copies/mL, 0.25% to 2.5% VAF) for metastatic breast cancer surveillance, using absolute molecular counting.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631504","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

SARCP, a Clinical Next-Generation Sequencing Assay for the Detection of Gene Fusions in Sarcomas: A Description of the First 652 Cases. SARCP，用于检测肉瘤基因融合的临床新一代测序测定：首批 652 例病例的描述。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-11-07 DOI: 10.1016/j.jmoldx.2024.10.004

Mazen A Atiq, Jagadheshwar Balan, Patrick R Blackburn, John M Gross, Jesse S Voss, Long Jin, Numrah Fadra, Jaime I Davila, Beth A Pitel, Simone Barreto Siqueira Parrilha Terra, Kay T Minn, Rory A Jackson, Christopher D Hofich, Kurt S Willkomm, Brenda J Peterson, Sydney N Clausen, Kandelaria M Rumilla, Sounak Gupta, Ying-Chun Lo, Cris M Ida, Jeremy F Molligan, Judith Jebastin Thangaiah, Matthew J Petersen, William R Sukov, Ruifeng Guo, Caterina Giannini, J Kenneth Schoolmeester, Karen Fritchie, Carrie Y Inwards, Andrew L Folpe, Andre M Oliveira, Jorge Torres-Mora, Benjamin R Kipp, Kevin C Halling

{"title":"SARCP, a Clinical Next-Generation Sequencing Assay for the Detection of Gene Fusions in Sarcomas: A Description of the First 652 Cases.","authors":"Mazen A Atiq, Jagadheshwar Balan, Patrick R Blackburn, John M Gross, Jesse S Voss, Long Jin, Numrah Fadra, Jaime I Davila, Beth A Pitel, Simone Barreto Siqueira Parrilha Terra, Kay T Minn, Rory A Jackson, Christopher D Hofich, Kurt S Willkomm, Brenda J Peterson, Sydney N Clausen, Kandelaria M Rumilla, Sounak Gupta, Ying-Chun Lo, Cris M Ida, Jeremy F Molligan, Judith Jebastin Thangaiah, Matthew J Petersen, William R Sukov, Ruifeng Guo, Caterina Giannini, J Kenneth Schoolmeester, Karen Fritchie, Carrie Y Inwards, Andrew L Folpe, Andre M Oliveira, Jorge Torres-Mora, Benjamin R Kipp, Kevin C Halling","doi":"10.1016/j.jmoldx.2024.10.004","DOIUrl":"10.1016/j.jmoldx.2024.10.004","url":null,"abstract":"<p><p>An amplicon-based targeted next-generation sequencing (NGS) assay for the detection of gene fusions in sarcomas was developed, validated, and implemented. This assay can detect fusions in targeted regions of 138 genes and BCOR internal tandem duplications. This study reviews our experience with testing on the first 652 patients analyzed. Gene fusions were detected in 238 (36.5%) of 652 cases, including 83 distinct fusions in the 238 fusion-positive cases, 10 of which had not been previously described. Among the 238 fusion-positive cases, the results assisted in establishing a diagnosis for 137 (58%) cases, confirmed a suspected diagnosis in 66 (28%) cases, changed a suspected diagnosis in 25 (10%) cases, and were novel fusions with unknown clinical significance in 10 (4%) cases. Twenty-six cases had gene fusions (ALK, ROS1, NTRK1, NTRK3, and COL1A1::PDGFB) for which there are targetable therapies. BCOR internal tandem duplications were identified in 6 (1.2%) of 485 patients. Among the 138 genes in the panel, 66 were involved in one or more fusions, and 72 were not involved in any fusions. There was little overlap between the genes involved as 5'-partners (31 different genes) and 3'-partners (37 different genes). This study shows the clinical utility of a next-generation sequencing gene fusion detection assay for the diagnosis and treatment of sarcomas.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631501","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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