Journal of Molecular Diagnostics最新文献_第6页

Tailored Digital PCR Follow-Up of Rare Fusion Transcripts after Initial Detection through RNA Sequencing in Hematological Malignancies 在血液恶性肿瘤中通过 RNA 测序初步检测到罕见融合转录本后，对其进行定制的数字 PCR 追踪。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-31 DOI: 10.1016/j.jmoldx.2024.07.004

Marie-Laure Boulland , Amyra Aliouat , Elie Jalaber , Anne Desmares , Saloua Toujani , Damien Luque Paz , Margaux Wiber , Emeline Voirin , Sébastien Lachot , Audrey Basinko , Wayne-Corentin Lambert , Sylvain Carras , Elie Cousin , Tony Marchand , Marie de Tayrac , Thierry Fest , Roch Houot , Cédric Pastoret

{"title":"Tailored Digital PCR Follow-Up of Rare Fusion Transcripts after Initial Detection through RNA Sequencing in Hematological Malignancies","authors":"Marie-Laure Boulland , Amyra Aliouat , Elie Jalaber , Anne Desmares , Saloua Toujani , Damien Luque Paz , Margaux Wiber , Emeline Voirin , Sébastien Lachot , Audrey Basinko , Wayne-Corentin Lambert , Sylvain Carras , Elie Cousin , Tony Marchand , Marie de Tayrac , Thierry Fest , Roch Houot , Cédric Pastoret","doi":"10.1016/j.jmoldx.2024.07.004","DOIUrl":"10.1016/j.jmoldx.2024.07.004","url":null,"abstract":"<div><div>Minimal residual disease (MRD) monitoring plays a pivotal role in the management of hematologic malignancies. Well-established molecular targets, such as <em>PML</em>::<em>RARA, CBFB::MYH11</em>, or <em>RUNX1</em>::<em>RUNX1T1</em>, are conventionally tracked by quantitative RT-PCR. Recently, a broader landscape of fusion transcripts has been unveiled through transcriptomic analysis. These newly discovered fusion transcripts may emerge as novel molecular markers for MRD quantification. In this study, we compared a targeted RNA-sequencing (RNA-seq) approach (FusionPlex) with a whole-transcriptomic strategy (Advanta RNA-Seq XT) for fusion detection in a training set of 21 samples. We evidenced a concordance of 100% for the detection of known fusions, and showed a good correlation for gene expression quantification between the two techniques (Spearman <em>r</em> = 0.77). Additionally, we prospectively evaluated the identification of fusions by targeted RNA-seq in a real-life series of 126 patients with hematological malignancy. At least one fusion transcript was detected for 60 patients (48%). We designed tailored digital PCR assays for 11 rare fusions, and validated this technique for MRD quantification with a limit of detection of <0.01%. The combination of RNA-seq and tailored digital PCR may become a new standard for MRD evaluation in patients lacking conventional molecular targets.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 11","pages":"Pages 1007-1017"},"PeriodicalIF":3.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057158","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

Genotype and Phenotype Correlation of the TPMT∗8 Allele in Thiopurine Metabolism TPMT*8：硫嘌呤代谢中一个重要的功能降低等位基因。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-31 DOI: 10.1016/j.jmoldx.2024.07.005

Rosalie M. Sterner, Patricia L. Hall, Dietrich Matern, John L. Black, Ann M. Moyer

{"title":"Genotype and Phenotype Correlation of the TPMT∗8 Allele in Thiopurine Metabolism","authors":"Rosalie M. Sterner, Patricia L. Hall, Dietrich Matern, John L. Black, Ann M. Moyer","doi":"10.1016/j.jmoldx.2024.07.005","DOIUrl":"10.1016/j.jmoldx.2024.07.005","url":null,"abstract":"<div><div>Thiopurine 6-mercaptopurine (6-MP) is metabolized by thiopurine methyl transferase (TPMT). <em>TPMT</em> genetic variation results in some individuals having reduced or absent TPMT enzyme activity. If these individuals take a full thiopurine dose, life-threatening adverse events can occur. Testing identifies patients with reduced or absent TPMT activity and is recommended before initiation of therapy. The <em>TPMT∗8</em> allele, defined by c.644G>A (p.Arg215His), is common among individuals of African ancestry (approximately 2.3% minor allele frequency) but is not included in genotyping recommendations due to its uncertain function. Here, a clinical TPMT enzyme activity assay was used to assess <em>TPMT</em> activity in red blood cells from 982 patients, including those with <em>∗1/∗8</em> (<em>n</em> = 22), <em>∗3A/∗8</em> (<em>n</em> = 1), and <em>∗3C/∗8</em> (<em>n</em> = 1) <em>TPMT</em> diplotypes. The average production of 6-methylmercaptopurine (primary TPMT product measured clinically) was 3.08 ± 0.16 nmol/mL per hour for <em>∗1/∗8</em> individuals, compared with 3.77 ± 0.03 nmol/mL per hour for normal metabolizers (<em>P</em> = 0.0001) and 2.39 ± 0.06 nmol 6-methylmercaptopurine/mL per hour for intermediate metabolizers (<em>P</em> < 0.0001). Individuals with a <em>TPMT∗1/∗8</em> diplotype displayed reduced 6-MP metabolism between that of normal metabolizers and intermediate metabolizers, suggesting that <em>TPMT∗8</em> is a reduced function allele.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 11","pages":"Pages 988-994"},"PeriodicalIF":3.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057160","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

Purity Independent Subtyping of Tumors (PurIST) Pancreatic Cancer Classifier PurIST 胰腺癌分类器：区分基础亚型和典型亚型的 16 种 RNA 表达特征的分析验证。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-22 DOI: 10.1016/j.jmoldx.2024.07.002

Yan Li , Jason D. Merker , Rachana Kshatriya , Dimitri G. Trembath , Ashley B. Morrison , Peyton C. Kuhlers , Naim U. Rashid , Jen Jen Yeh , Margaret L. Gulley

{"title":"Purity Independent Subtyping of Tumors (PurIST) Pancreatic Cancer Classifier","authors":"Yan Li , Jason D. Merker , Rachana Kshatriya , Dimitri G. Trembath , Ashley B. Morrison , Peyton C. Kuhlers , Naim U. Rashid , Jen Jen Yeh , Margaret L. Gulley","doi":"10.1016/j.jmoldx.2024.07.002","DOIUrl":"10.1016/j.jmoldx.2024.07.002","url":null,"abstract":"<div><div>The two major molecular subtypes of pancreatic adenocarcinoma reportedly have differential response to FOLFIRINOX-based therapy. To promote rapid assignment of basal versus classical subtypes, an array-based single-sample classifier assay was developed and applied to 74 formalin-fixed, paraffin-embedded biopsy or resection specimens of known subtype based on transcriptomics. The Purity Independent Subtyping of Tumors (PurIST) algorithm assigns subtype based on relative expression of 16 RNAs counted by RNA sequencing (RNAseq) versus more practical array-based NanoString nCounter Elements XT technology. Subtype calls were largely concordant between RNAseq and array methods (72/74, 97% agreement). Compared with the lengthy RNAseq protocol, the array-based assay takes just 3 working days to analyze, permitting rapid reporting of tumor subtype. In conclusion, the PurIST pancreatic cancer classifier has robust performance to classify pancreatic adenocarcinoma into basal versus classical subtypes. Clinical validation studies are underway to evaluate outcome in patients whose standard-of-care chemotherapy regimen is selected on the basis of rapid subtype assignment (<span><span>NCT04683315</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 11","pages":"Pages 962-970"},"PeriodicalIF":3.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057157","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

Performance Characteristics of Next-Generation Sequencing–Based Engraftment Monitoring and Microchimerism Detection in Allogeneic Hematopoietic Cell Transplantation 异基因造血细胞移植中基于 NGS 的移植监测和微嵌合体检测的性能特征：临床检测验证的实用方法》。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-22 DOI: 10.1016/j.jmoldx.2024.07.003

Amanda G. Blouin , Wyatt Nelson , Daniel Geraghty , Medhat Askar , Fei Ye

{"title":"Performance Characteristics of Next-Generation Sequencing–Based Engraftment Monitoring and Microchimerism Detection in Allogeneic Hematopoietic Cell Transplantation","authors":"Amanda G. Blouin , Wyatt Nelson , Daniel Geraghty , Medhat Askar , Fei Ye","doi":"10.1016/j.jmoldx.2024.07.003","DOIUrl":"10.1016/j.jmoldx.2024.07.003","url":null,"abstract":"<div><div>Chimerism analysis by next-generation sequencing (NGS) is an emerging method for engraftment monitoring after allogeneic hematopoietic cell transplantation. A high-sensitivity method is required for the detection of microchimerism (<1% chimerism), which may have clinical utility in early relapse detection, allograft monitoring in organ transplantation, and other allogeneic cellular therapies (such as microtransplantations). As more clinical laboratories adopt this method, a thorough assessment of performance is needed. This study evaluated one such NGS-based assay that uses both single-nucleotide polymorphisms and insertions/deletions as genetic markers. An assessment of accuracy, linearity, sensitivity, and reproducibility was performed. Analytical sensitivity was 0.2% donor for single donor and 0.5% donors for double donors. The assay showed a high degree of reproducibility over a full range of chimerism. Comparison to short-tandem-repeat (STR) PCR showed high concordance; yet <5% chimerism was consistently detected by NGS, but not by STR-PCR. Comparison to real-time quantitative PCR showed high concordance, but with lower correlation in the midrange (40% to 60% chimerism). Overall, the assay showed consistent performance with high sensitivity and accuracy compared with STR-PCR and real-time quantitative PCR across a full range of chimerism in the setting of single-donor and multidonor transplantations. In addition, criteria for quality metrics were established for sequencing performance and data analysis and considerations made for clinical laboratory validation of NGS-based chimerism assay and analysis software.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 11","pages":"Pages 995-1006"},"PeriodicalIF":3.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057156","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

The Correlation between Plasma Circulating Tumor DNA and Radiographic Tumor Burden 血浆循环肿瘤 DNA 与放射肿瘤负荷之间的相关性。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-22 DOI: 10.1016/j.jmoldx.2024.07.001

Evan M. Alexander , Hunter A. Miller , Michael E. Egger , Melissa L. Smith , Kavitha Yaddanapudi , Mark W. Linder

{"title":"The Correlation between Plasma Circulating Tumor DNA and Radiographic Tumor Burden","authors":"Evan M. Alexander , Hunter A. Miller , Michael E. Egger , Melissa L. Smith , Kavitha Yaddanapudi , Mark W. Linder","doi":"10.1016/j.jmoldx.2024.07.001","DOIUrl":"10.1016/j.jmoldx.2024.07.001","url":null,"abstract":"<div><div>Conventional blood-based biomarkers and radiographic imaging are excellent for use in monitoring different aspects of malignant disease, but given their specific shortcomings, their integration with other, complementary markers such as plasma circulating tumor DNA (ctDNA) will be beneficial toward a precision medicine–driven future. Plasma ctDNA analysis utilizes the measurement of cancer-specific molecular alterations in a variety of bodily fluids released by dying tumor cells to monitor and profile response to therapy, and is being employed in several clinical scenarios. Plasma concentrations of ctDNA have been reported to correlate with tumor burden. However, the strength of this association is generally poor and highly variable, confounding the interpretation of longitudinal plasma ctDNA measurements in conjunction with routine radiographic assessments. Herein is discussed what is currently understood with respect to the fundamental characteristics of tumor growth that dictate plasma ctDNA concentrations, with a perspective on its interpretation in conjunction with radiographically determined tumor burden assessments.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 11","pages":"Pages 952-961"},"PeriodicalIF":3.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057159","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

Open-Source Bioinformatic Pipeline to Improve PMS2 Genetic Testing Using Short-Read NGS Data 利用短读数 NGS 数据改进 PMS2 基因测试的开源生物信息学管道。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.05.005

{"title":"Open-Source Bioinformatic Pipeline to Improve PMS2 Genetic Testing Using Short-Read NGS Data","authors":"","doi":"10.1016/j.jmoldx.2024.05.005","DOIUrl":"10.1016/j.jmoldx.2024.05.005","url":null,"abstract":"<div><p>The molecular diagnosis of mismatch repair–deficient cancer syndromes is hampered by difficulties in sequencing the <em>PMS2</em> gene, mainly owing to the PMS2CL pseudogene. Next-generation sequencing short reads cannot be mapped unambiguously by standard pipelines, compromising variant calling accuracy. This study aimed to provide a refined bioinformatic pipeline for <em>PMS2</em> mutational analysis and explore <em>PMS2</em> germline pathogenic variant prevalence in an unselected hereditary cancer (HC) cohort. <em>PMS2</em> mutational analysis was optimized using two cohorts: 192 unselected HC patients for assessing the allelic ratio of paralogous sequence variants, and 13 samples enriched with <em>PMS2</em> (likely) pathogenic variants screened previously by long-range genomic DNA PCR amplification. Reads were forced to align with the <em>PMS2</em> reference sequence, except those corresponding to exon 11, where only those intersecting gene-specific invariant positions were considered. Afterward, the refined pipeline's accuracy was validated in a cohort of 40 patients and used to screen 5619 HC patients. Compared with our routine diagnostic pipeline, the PMS2_vaR pipeline showed increased technical sensitivity (0.853 to 0.956, respectively) in the validation cohort, identifying all previously <em>PMS2</em> pathogenic variants found by long-range genomic DNA PCR amplification. Fifteen HC cohort samples carried a pathogenic <em>PMS2</em> variant (15 of 5619; 0.285%), doubling the estimated prevalence in the general population. The refined open-source approach improved <em>PMS2</em> mutational analysis accuracy, allowing its inclusion in the routine next-generation sequencing pipeline streamlining <em>PMS2</em> screening.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 8","pages":"Pages 727-738"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001181/pdfft?md5=91683b4368460b158919e0c187d84829&pid=1-s2.0-S1525157824001181-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293860","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

Accuracy of cobas MTB and MTB-RIF/INH for Detection of Mycobacterium tuberculosis and Drug Resistance cobas MTB 和 MTB-RIF/INH 检测结核杆菌和耐药性的准确性。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.05.004

{"title":"Accuracy of cobas MTB and MTB-RIF/INH for Detection of Mycobacterium tuberculosis and Drug Resistance","authors":"","doi":"10.1016/j.jmoldx.2024.05.004","DOIUrl":"10.1016/j.jmoldx.2024.05.004","url":null,"abstract":"<div><p>This study evaluated the performance of cobas MTB and cobas MTB-RIF/INH for the diagnosis of tuberculosis and detection of rifampicin (RIF) and isoniazid (INH) resistance. Adults presenting with pulmonary tuberculosis symptoms were recruited in South Africa, Moldova, and India. Performance of cobas MTB was assessed against culture, whereas cobas MTB-RIF/INH was assessed using phenotypic drug susceptibility testing and whole-genome sequencing as composite reference standards. Xpert MTB/RIF (Xpert) or Xpert MTB/RIF Ultra (Ultra) was used as a comparator. The overall sensitivity and specificity of cobas MTB were 95% (95% CI, 93%–96%) and 96% (95% CI, 95%–97%). Among smear-negatives, the sensitivity of cobas MTB was 75% (95% CI, 66%–83%). Among participants tested with both cobas MTB and Xpert, sensitivity was 96% (95% CI, 94%–97%) for cobas MTB and 95% (95% CI, 93%–97%) for Xpert. Among participants tested with both cobas MTB and Ultra, sensitivity was 88% (95% CI, 81%–92%) for cobas MTB and 89% (95% CI, 83%–93%) for Ultra. Sensitivity and specificity of cobas MTB-RIF/INH for RIF and INH detection were 90% (95% CI, 84%–94%) and 100% (95% CI, 99%–100%), and 89% (95% CI, 84%–93%) and 99.5% (95% CI, 98%–100%), respectively. The cobas MTB and cobas MTB-RIF/INH assays exhibited high performance in a diverse population and present a suitable option for molecular detection of tuberculosis and RIF and INH resistance.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 8","pages":"Pages 708-718"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293830","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

Analytical Validation of the Multitarget Stool RNA Test for Colorectal Cancer Screening 用于大肠癌筛查的多靶点粪便 RNA 检测的分析验证。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.05.001

Erica K. Barnell , Jack Land , Kimberly Kruse , Maya C. Scott , Ben Wedeking , Catherine Morrison , Clayton Grass , Ann Zuniga , Elizabeth M. Wurtzler , Eric J. Duncavage

{"title":"Analytical Validation of the Multitarget Stool RNA Test for Colorectal Cancer Screening","authors":"Erica K. Barnell , Jack Land , Kimberly Kruse , Maya C. Scott , Ben Wedeking , Catherine Morrison , Clayton Grass , Ann Zuniga , Elizabeth M. Wurtzler , Eric J. Duncavage","doi":"10.1016/j.jmoldx.2024.05.001","DOIUrl":"10.1016/j.jmoldx.2024.05.001","url":null,"abstract":"<div><p>The multitarget stool RNA (mt-sRNA) test (ColoSense) is a noninvasive diagnostic test that screens for colorectal cancer and advanced adenomas in average-risk individuals aged 45 years and older. The mt-sRNA test incorporates a commercially available fecal immunochemical test, concentration of eight RNA transcripts, and participant-reported smoking status. As part of the CRC-PREVENT (Colorectal Cancer and Pre-Cancerous Adenoma Non-Invasive Detection Test) clinical trial, 12 analytical validation studies were conducted to assess analytical sensitivity, linearity, precision, interfering substances, cross-reactivity, carry-over, cross-contamination, and robustness. Analytical validation of the mt-sRNA test demonstrated limit of blank, limit of detection, and limit of quantification of <0.6, <0.7, and ≤2.5 copies/μL for all markers, respectively. The mt-sRNA test demonstrated linearity between 2.5 and 2500 copies/μL, and <20% coefficient of variation, and/or ≥95% concordance with regard to precision, interfering substances, carry-over, cross-contamination, and robustness. There was no significant impact of cross-reactivity from non–colorectal cancer diseases. These data provide a framework for laboratories to complete analytical validation for RNA-based panels that require premarket approval as a class III medical device from the US Food and Drug Administration.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 8","pages":"Pages 700-707"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001004/pdfft?md5=5a002dccd0c0f55c43f0c66aa9dd43d4&pid=1-s2.0-S1525157824001004-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604443","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

Economic Impact of Whole Genome Sequencing and Whole Transcriptome Sequencing Versus Routine Diagnostic Molecular Testing to Stratify Patients with B-Cell Acute Lymphoblastic Leukemia 全基因组测序和全转录组测序与常规诊断分子检测对 B 细胞急性淋巴细胞白血病患者分层的经济影响。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.04.006

Martin Vu , Koen Degeling , Georgina L. Ryland , Oliver Hofmann , Ashley P. Ng , David Westerman , Maarten J. IJzerman

{"title":"Economic Impact of Whole Genome Sequencing and Whole Transcriptome Sequencing Versus Routine Diagnostic Molecular Testing to Stratify Patients with B-Cell Acute Lymphoblastic Leukemia","authors":"Martin Vu , Koen Degeling , Georgina L. Ryland , Oliver Hofmann , Ashley P. Ng , David Westerman , Maarten J. IJzerman","doi":"10.1016/j.jmoldx.2024.04.006","DOIUrl":"10.1016/j.jmoldx.2024.04.006","url":null,"abstract":"<div><p>Whole genome and whole transcriptome sequencing (WGTS) can accurately distinguish B-cell acute lymphoblastic leukemia (B-ALL) genomic subtypes. However, whether this is economically viable remains unclear. This study compared the direct costs and molecular subtype classification yield using different testing strategies for WGTS in adolescent and young adult/adult patients with B-ALL. These approaches were: (1) combined <em>BCR::ABL1</em> by fluorescence <em>in situ</em> hybridization (FISH) + WGTS for all patients; and (2) sequential <em>BCR::ABL1</em> FISH + WGTS contingent on initial <em>BCR::ABL1</em> FISH test outcome. The cost of routine diagnostic testing was estimated using Medicare or hospital fees, and the additional cost of WGTS was evaluated from the health care provider perspective using time-driven activity-based costing with resource identification elicited from experts. Molecular subtype classification yield data were derived from literature sources. Parameter uncertainty was assessed through deterministic sensitivity analysis; additional scenario analyses were performed. The total per patient cost of WGTS was $4319 (all costs reported in US dollars); consumables accounted for 74% of the overall cost, primarily driven by sequencing-related consumables. The incremental cost per additional patient categorized into molecular subtype was $8498 for combined <em>BCR::ABL1</em> FISH + WGTS for all patients and $5656 for initial <em>BCR::ABL1</em> FISH + WGTS for select patients compared with routine diagnostic testing. A reduction in the consumable costs of WGTS or an increase in the yield of molecular subtype classification is favorable.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 8","pages":"Pages 673-684"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767957","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

Recommendations for Tumor Mutational Burden Assay Validation and Reporting 肿瘤突变负荷测定验证和报告建议：分子病理学协会、美国病理学家学会和癌症免疫疗法学会的联合共识建议》（Association for Molecular Pathology, College of American Pathologists, and Society for Immunotherapy of Cancer）。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2024-08-01 DOI: 10.1016/j.jmoldx.2024.05.002

{"title":"Recommendations for Tumor Mutational Burden Assay Validation and Reporting","authors":"","doi":"10.1016/j.jmoldx.2024.05.002","DOIUrl":"10.1016/j.jmoldx.2024.05.002","url":null,"abstract":"<div><p>Tumor mutational burden (TMB) has been recognized as a predictive biomarker for immunotherapy response in several tumor types. Several laboratories offer TMB testing, but there is significant variation in how TMB is calculated, reported, and interpreted among laboratories. TMB standardization efforts are underway, but no published guidance for TMB validation and reporting is currently available. Recognizing the current challenges of clinical TMB testing, the Association for Molecular Pathology convened a multidisciplinary collaborative working group with representation from the American Society of Clinical Oncology, the College of American Pathologists, and the Society for the Immunotherapy of Cancer to review the laboratory practices surrounding TMB and develop recommendations for the analytical validation and reporting of TMB testing based on survey data, literature review, and expert consensus. These recommendations encompass pre-analytical, analytical, and postanalytical factors of TMB analysis, and they emphasize the relevance of comprehensive methodological descriptions to allow comparability between assays.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 8","pages":"Pages 653-668"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824001156/pdfft?md5=1f258a6b15d6b3f5b04704ed658b82e9&pid=1-s2.0-S1525157824001156-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293862","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