Journal of Molecular Diagnostics最新文献

The Validation of Digital PCR–Based Minimal Residual Disease Detection for the Common Mutations in IDH1 and IDH2 Genes in Patients with Acute Myeloid Leukemia 基于数字pcr的IDH1和IDH2基因常见突变的最小残留疾病检测在急性髓系白血病患者中的验证

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-01 DOI: 10.1016/j.jmoldx.2024.11.002

Jing Di , Tao Sheng , Ranjana Arora , Jennifer Stocks-Candelaria , Sainan Wei , Charles Lutz , Fevzi F. Yalniz , Shulin Zhang

{"title":"The Validation of Digital PCR–Based Minimal Residual Disease Detection for the Common Mutations in IDH1 and IDH2 Genes in Patients with Acute Myeloid Leukemia","authors":"Jing Di , Tao Sheng , Ranjana Arora , Jennifer Stocks-Candelaria , Sainan Wei , Charles Lutz , Fevzi F. Yalniz , Shulin Zhang","doi":"10.1016/j.jmoldx.2024.11.002","DOIUrl":"10.1016/j.jmoldx.2024.11.002","url":null,"abstract":"<div><div>Accurate monitoring of minimal residual disease (MRD) is crucial for effective management of patients with acute myeloid leukemia (AML). This study aims to validate MRD detection of the seven most common <em>IDH1</em> and <em>IDH2</em> mutations in patients with AML using a QuantStudio 3D digital PCR platform. This assay demonstrated a high concordance for the variant allele frequencies between digital PCR and next-generation sequencing assays. Precision analysis revealed only small variation (<0.5 log10) for all mutations near or at the limit of detection level. This validation also showed a great reproducibility for interrun and intrarun comparisons (28 runs, variation ranges from 0 to 0.48 log10), ensuring comparable results for patient follow-ups. The limit of detection was determined to be 0.1% for all mutations, except the <em>IDH2 R140Q</em> mutation, which was 0.5%. Controls and acceptable ranges were also established for each mutation during validation. This study suggests that the QuantStudio 3D digital PCR assay is a quantitative, sensitive, and reproducible platform for monitoring MRD in patients with AML.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 2","pages":"Pages 100-108"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774302","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

Validation and Performance of Quantitative BRCA1 and RAD51C Promoter Hypermethylation Testing in Breast and Ovarian Cancers 乳腺癌和卵巢癌 BRCA1 和 RAD51C Promoter 高甲基化定量检测的验证和性能。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-01 DOI: 10.1016/j.jmoldx.2024.11.004

J. Lynn Fink , Binny Jaradi , Nathan Stone , Brittany Sanker , Fan Zhang , Alexander Dobrovic , Sophie Kirschner , James Hadfield , Olga Kondrashova , Paul M. Waring

{"title":"Validation and Performance of Quantitative BRCA1 and RAD51C Promoter Hypermethylation Testing in Breast and Ovarian Cancers","authors":"J. Lynn Fink , Binny Jaradi , Nathan Stone , Brittany Sanker , Fan Zhang , Alexander Dobrovic , Sophie Kirschner , James Hadfield , Olga Kondrashova , Paul M. Waring","doi":"10.1016/j.jmoldx.2024.11.004","DOIUrl":"10.1016/j.jmoldx.2024.11.004","url":null,"abstract":"<div><div>Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors represent a significant advancement in the treatment of epithelial ovarian cancer, triple-negative breast cancer, pancreatic cancer, and castrate-resistant prostate cancer, and they are poised to improve treatment in an increasing number of other cancer types. PARP inhibitor efficacy as monotherapy has been primarily observed in tumors with deleterious genetic variants in genes involved in the homologous recombination repair pathway. Tumors without these variants have also been shown to respond; notably, those with hypermethylation at all alleles of the <em>BRCA1</em> or <em>RAD51C</em> promoter can respond to PARP inhibitors. These epigenetic biomarkers therefore represent a patient population that may also benefit from this targeted therapy. However, no robust test has been conducted to identify these biomarkers in routine clinical specimens that is amenable to implementation for decentralized testing. This study describes the analytical and clinical validation of a <em>BRCA1</em> and <em>RAD51C</em> promoter methylation test that can be run with a single-day library preparation workflow for sequencing on any next-generation sequencing platform. The results show that this test can accurately quantitate the level of promoter methylation at the <em>BRCA1</em> and <em>RAD51C</em> genes using formalin-fixed, paraffin-embedded samples, even when the extracted DNA is extremely degraded or the input amount is limited. This test increases the precision of diagnostic tests aimed at identifying patients who are likely and unlikely to respond to PARP inhibitor therapy.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 2","pages":"Pages 139-153"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830686","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

Investigating the Pathogenicity of Uncommon KRAS Mutations and Their Association with Clinicopathologic Characteristics in Patients with Colorectal Cancer 探讨结直肠癌患者罕见KRAS突变的致病性及其与临床病理特征的关系。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-01 DOI: 10.1016/j.jmoldx.2024.11.007

Riccardo Adorisio , Davide Ciardiello , Alessandra Rappa , Lorenzo Gervaso , Gloria Pelizzari , Laura Marinucci , Nicola Fusco , Maria Giulia Zampino , Nicola Fazio , Konstantinos Venetis , Elena Guerini-Rocco

{"title":"Investigating the Pathogenicity of Uncommon KRAS Mutations and Their Association with Clinicopathologic Characteristics in Patients with Colorectal Cancer","authors":"Riccardo Adorisio , Davide Ciardiello , Alessandra Rappa , Lorenzo Gervaso , Gloria Pelizzari , Laura Marinucci , Nicola Fusco , Maria Giulia Zampino , Nicola Fazio , Konstantinos Venetis , Elena Guerini-Rocco","doi":"10.1016/j.jmoldx.2024.11.007","DOIUrl":"10.1016/j.jmoldx.2024.11.007","url":null,"abstract":"<div><div>Kirsten rat sarcoma viral oncogene homolog <em>(KRAS</em>) somatic mutations occur in 30% to 40% of patients with colorectal cancer (CRC). These were thought to equally affect prognosis and resistance to anti–epidermal growth factor receptor agents; however, recent data show the activity of KRAS-G12C and pan-RAS inhibitors. The effects of uncommon <em>KRAS</em> (u<em>KRAS</em>) variants are largely unexplored. The distribution and pathogenicity of u<em>KRAS</em> mutations and their relationship with patients’ clinicopathologic features were assessed. A total of 2427 CRCs were profiled for <em>KRAS</em> using next-generation sequencing (NGS). The study and control groups included patients with u<em>KRAS</em> (<1% frequency in CRC data sets on cBioPortal) and canonical <em>KRAS</em> mutations, respectively. <em>In silico</em> protein structure modifications and prediction analyses were performed by using PyMOL, trRosetta, and PolyPhen-2. u<em>KRAS</em> mutations affected 35 cases (1.5%), with G13C (28.6%), G12R (20%), and V14I (8.6%) being most common. Missense mutations (D33E, G12W, G12F, Q22H, Q61L, and L19F) occurred in nine cases (25.7%). Duplications (G10dup and L52_G60dup) affected two cases. Pathogenicity analyses showed that G12W, Q22R, L56V, and A130I mutations are probably damaging, with scores between 0.928 and 1.000. No differences were seen in clinicopathologic features. u<em>KRAS</em> mutants had lower event-free survival but no difference in overall survival compared with controls. Although these data are hypothesis generating and need further confirmation, they highlight the importance of NGS-based profiling to identify CRC patients with u<em>KRAS</em> mutations as candidates for personalized therapy.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 2","pages":"Pages 130-138"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856521","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

Clinical Implementation of a High-Throughput Automated Comprehensive Genomic Profiling Test 高通量自动化综合基因组分析测试 - TruSight Oncology 500 HT 的临床实施。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-01 DOI: 10.1016/j.jmoldx.2024.11.005

Markus Ball , Eva Romanovsky , Fabian Schnecko , Martina Kirchner , Olaf Neumann , Regine Brandt , Susanne Beck , Huriye Seker-Cin , Klaus Kluck , Iordanis Ourailidis , Hannah Goldschmid , Annette Fink , Anna-Lena Volckmar , Michael Menzel , Michael Allgäuer , Peter Schirmacher , Jan Budczies , Albrecht Stenzinger , Daniel Kazdal

{"title":"Clinical Implementation of a High-Throughput Automated Comprehensive Genomic Profiling Test","authors":"Markus Ball , Eva Romanovsky , Fabian Schnecko , Martina Kirchner , Olaf Neumann , Regine Brandt , Susanne Beck , Huriye Seker-Cin , Klaus Kluck , Iordanis Ourailidis , Hannah Goldschmid , Annette Fink , Anna-Lena Volckmar , Michael Menzel , Michael Allgäuer , Peter Schirmacher , Jan Budczies , Albrecht Stenzinger , Daniel Kazdal","doi":"10.1016/j.jmoldx.2024.11.005","DOIUrl":"10.1016/j.jmoldx.2024.11.005","url":null,"abstract":"<div><div>The adoption of comprehensive genomic profiling in oncology has rapidly increased the demand for standardized tumor sample processing in diagnostic laboratories. Automation of DNA and RNA library preparation workflows offers the possibility to scale-up and standardize sample processing. We report on the clinical implementation of the automated TruSight Oncology 500 High-Throughput library preparation workflow from formalin-fixed, paraffin-embedded tumor samples using the Biomek i7 hybrid Workstation. Using the same input amount, the automated workflow was validated against manual library preparation. Quality control metrics (total and mapped reads, median insert size, and median exon coverage) and the detection of tumor mutational burden, a complex biomarker, were concordant between the manual and automated workflows. The automated workflow was implemented on a total of 2997 pan-cancer clinical samples to detect genomic variants and complex biomarkers. Workflow automation resulted in a 4-fold reduction in hands-on time and a 1.7-fold reduction in total runtime compared with manual library preparation (6 hours vs. 23 hours; 24 hours vs. 42.5 hours, respectively) for a 48 DNA + 48 RNA sample batch. The automated workflow required one technician versus three technicians to manually prepare the same number of libraries. This study shows that implementation of the automated TruSight Oncology 500 High-Throughput workflow significantly reduced hands-on time and processing time per sample compared with manual library preparation.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 2","pages":"Pages 154-162"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824659","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 and Clinical Validation of the Plasma-Based Guardant360 CDx Test for Assessing HER2 (ERBB2) Mutation Status in Patients with Non–Small-Cell Lung Cancer for Treatment with Trastuzumab Deruxtecan in DESTINY-Lung01/02

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-01 DOI: 10.1016/j.jmoldx.2024.11.006

Zhenhao Qi , Shinya Tokuhiro , Justin I. Odegaard , Sara Wienke , Maha Karnoub , Wenqin Feng , Ryota Shiga , Egbert F. Smit , Yasushi Goto , Adrianus J. De Langen , Koichi Goto , Kaline Pereira , Shirin Khambata-Ford

{"title":"Analytical and Clinical Validation of the Plasma-Based Guardant360 CDx Test for Assessing HER2 (ERBB2) Mutation Status in Patients with Non–Small-Cell Lung Cancer for Treatment with Trastuzumab Deruxtecan in DESTINY-Lung01/02","authors":"Zhenhao Qi , Shinya Tokuhiro , Justin I. Odegaard , Sara Wienke , Maha Karnoub , Wenqin Feng , Ryota Shiga , Egbert F. Smit , Yasushi Goto , Adrianus J. De Langen , Koichi Goto , Kaline Pereira , Shirin Khambata-Ford","doi":"10.1016/j.jmoldx.2024.11.006","DOIUrl":"10.1016/j.jmoldx.2024.11.006","url":null,"abstract":"<div><div>This study demonstrates the analytical and clinical validity of the approved (United States and Japan) plasma-based Guardant360 companion diagnostic (CDx) test for selecting patients with human epidermal growth factor receptor 2 (<em>HER2</em> [<em>ERBB2</em>])–mutated (<em>HER2</em>m) non–small-cell lung cancer (NSCLC) for trastuzumab deruxtecan (T-DXd) treatment. Concordance between the Guardant360 CDx test and the plasma-based AVENIO ctDNA Expanded Kit Assay (AVENIO), as well as the tissue-based clinical trial assays (CTAs) was investigated. Clinical utility was assessed by comparing T-DXd clinical efficacy results of patients in DESTINY-Lung01/02 who tested positive for <em>HER2</em> mutations using the Guardant360 CDx test to benchmark efficacy results from DESTINY-Lung01/02. Finally, concordance between the Guardant360 CDx test and the tissue-based Oncomine Dx Target (ODxT) test was explored. High concordance was observed between the Guardant360 CDx test versus AVENIO [positive percent agreement (PPA), 98.8%; negative percent agreement (NPA), 91.5%] and CTAs (DESTINY-Lung01 Cohort 2—PPA, 91.0%; NPA, 100%; DESTINY-Lung02 arm 1—PPA, 86.0%; NPA, 100%). Confirmed objective response rates were similar in patients with <em>HER2</em>m NSCLC identified by the Guardant360 CDx test and by CTAs. There was a high level of agreement between the Guardant360 CDx test and the ODxT test. The Guardant360 CDx test demonstrated analytical and clinical validity for identifying patients with <em>HER2</em>m NSCLC for T-DXd therapy; results support plasma-based testing when tissue-based testing is not feasible.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 2","pages":"Pages 119-129"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068681","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

Developments in Infectious Disease Molecular Diagnostics and the Impact on Health Care 传染病分子诊断的发展及其对医疗保健的影响。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-01 DOI: 10.1016/j.jmoldx.2024.06.014

Ryan F. Relich , Kirsten St. George , Heba H. Mostafa , Erin H. Graf , Association for Molecular Pathology Infectious Disease Subdivision Leadership

引用次数: 0

BCR::ABL1 Deep Molecular Response Quantification and Transcript Type Identification in Chronic Myeloid Leukemia Using a US Food and Drug Administration–Approved Droplet-Based Digital PCR Assay 使用美国食品和药物管理局批准的基于液滴的数字PCR检测慢性髓性白血病BCR: ABL1深度分子反应定量和转录物类型鉴定

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-02-01 DOI: 10.1016/j.jmoldx.2024.11.003

Camille Kockerols , Peter J.M. Valk , Pauline Hogenbirk , Jan J. Cornelissen , Peter E. Westerweel

{"title":"BCR::ABL1 Deep Molecular Response Quantification and Transcript Type Identification in Chronic Myeloid Leukemia Using a US Food and Drug Administration–Approved Droplet-Based Digital PCR Assay","authors":"Camille Kockerols , Peter J.M. Valk , Pauline Hogenbirk , Jan J. Cornelissen , Peter E. Westerweel","doi":"10.1016/j.jmoldx.2024.11.003","DOIUrl":"10.1016/j.jmoldx.2024.11.003","url":null,"abstract":"<div><div><em>BCR</em>::<em>ABL1</em> digital PCR is a promising technique for the quantification of deep molecular responses (DMRs) in chronic myeloid leukemia. It provides an improved precision and sensitivity compared with conventional real-time quantitative PCR (qPCR), which is particularly relevant in the context of prediction of successful treatment-free remission. This study assessed the feasibility of <em>BCR</em>::<em>ABL1</em> digital PCR in clinical practice. A total of 168 DMR samples of patients with chronic myeloid leukemia aiming for a treatment-free remission attempt were assessed by both digital PCR and qPCR. Digital PCR was performed with the droplet-based Bio-Rad QXDx BCR-ABL %IS assay, using eight replicates per sample. qPCR was performed with the fully automized Cepheid Xpert BCR-ABL Ultra assay. Various technical and practical aspects of <em>BCR</em>::<em>ABL1</em> quantification using digital PCR were assessed. The reported limit of detection of the qPCR is molecular response 4.5, requiring an equivalent of 32,000 <em>ABL1</em> transcripts. Using digital PCR, a median number of <em>ABL1</em> of approximately 300,000 were obtained. <em>BCR</em>::<em>ABL1</em> was quantifiable by digital PCR in 68% of the samples below qPCR's limit of detection. In addition, e13a2 and e14a2 <em>BCR</em>::<em>ABL1</em> transcript types could be discriminated based on the mean fluorescence intensity of <em>BCR</em>::<em>ABL1</em>-positive droplets. <em>BCR</em>::<em>ABL1</em> digital PCR is feasible for DMR quantification in clinical practice and offers an increased sensitivity over qPCR.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 2","pages":"Pages 109-118"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774371","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

Clinical Validation of the TruSight Oncology 500 Assay for the Detection and Reporting of Pan- Cancer Biomarkers.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-01-31 DOI: 10.1016/j.jmoldx.2025.01.002

Hussam Al-Kateb, Shannon M Knight, Gopinath Sivasankaran, Jesse S Voss, Beth A Pitel, Joseph H Blommel, Calvin R Jerde, Kandeleria M Rumilla, Jodi L Lee, Nate R Mattson, Kim P Lauer, Eric A Zimmerman Zuckerman, Chris D Hofich, Dragana Milosevic, Joe Thompson, Lori S Tillmans, Tony T Stai, Surendra Dasari, Amber L Pryzbylski, Lisa G Mullineaux, Cris M Ida, Robert B Jenkins, Sounak Gupta, Benjamin R Kipp, Kevin C Halling

{"title":"Clinical Validation of the TruSight Oncology 500 Assay for the Detection and Reporting of Pan- Cancer Biomarkers.","authors":"Hussam Al-Kateb, Shannon M Knight, Gopinath Sivasankaran, Jesse S Voss, Beth A Pitel, Joseph H Blommel, Calvin R Jerde, Kandeleria M Rumilla, Jodi L Lee, Nate R Mattson, Kim P Lauer, Eric A Zimmerman Zuckerman, Chris D Hofich, Dragana Milosevic, Joe Thompson, Lori S Tillmans, Tony T Stai, Surendra Dasari, Amber L Pryzbylski, Lisa G Mullineaux, Cris M Ida, Robert B Jenkins, Sounak Gupta, Benjamin R Kipp, Kevin C Halling","doi":"10.1016/j.jmoldx.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2025.01.002","url":null,"abstract":"<p><p>The TruSight Oncology 500 (TSO500) High-Throughput is a genomic profiling assay (Illumina, Inc.), supported by a bioinformatic analysis pipeline to evaluate somatic SNV/DELINS, gene amplification (GA), microsatellite instability (MSI), tumor mutational burden (TMB), gene fusion (GF), and splice variants (SV) in solid tumors. This study outlines the approach used by the Genomics Laboratory at the Mayo Clinic to evaluate the technical performance of TSO500. The assessment involved 104 DNA and 223 RNA samples extracted from over 20 tumor types. The assay demonstrated robust performance using 40 ng of input DNA and RNA, with slightly improved results observed at 60 ng of input DNA. Tumor percentage (TP) significantly influenced assay performance, with all variants being detected at 93% and 85% and above at TP >50% and >20%, respectively. Precision exceeded 93% across all variant types, including SNVs and DELINS with a variant allele frequency of ≥5%. Accuracy was ≥97% for all variant types except for TMB, which was 83.3% when compared to the reference method (Foundation Medicine). Most discordant TMB cases had scores in the range of 8-12 mutations per megabase. Overall, the TSO500 assay demonstrated strong performance and reliable accuracy in detecting the evaluated markers.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081900","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

Pharmacogenetic Testing in Admixed Populations: Frequency of the Association for Molecular Pathology Pharmacogenomics Working Group Tier 1 Variant Alleles in Brazilians.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-01-23 DOI: 10.1016/j.jmoldx.2024.12.011

Guilherme Suarez-Kurtz

{"title":"Pharmacogenetic Testing in Admixed Populations: Frequency of the Association for Molecular Pathology Pharmacogenomics Working Group Tier 1 Variant Alleles in Brazilians.","authors":"Guilherme Suarez-Kurtz","doi":"10.1016/j.jmoldx.2024.12.011","DOIUrl":"10.1016/j.jmoldx.2024.12.011","url":null,"abstract":"<p><p>This article examines the frequency distribution of tier 1 pharmacogenetic variants of the Association for Molecular Pathology Pharmacogenomics Working Group Recommendations in two large (>1000 individuals) cohorts of the admixed Brazilian population, and in patients from the Brazilian Public Health System enrolled in pharmacogenetic trials. Three tier 1 variants, all in DPYD, were consistently absent, which may justify their noninclusion in genotyping panels for Brazilians; 13 variants had frequency ≤1.0%, and the remaining 21 variants ranged in frequency from 1.2% (NUDT15∗3) to 76.4% (CYP3A5∗3). The frequency of some CYP2C9, CYP2D6, CYP3A4, and VKORC1 variants differed significantly across the three major race/color categories of the Brazilian Census (White, Brown, and Black), as a consequence of different proportions of individual European and African ancestry. However, it is recommended that selection of variants for inclusion in pharmacogenetic testing panels and implementation of pharmacogenetic-informed dosing guidelines for Brazilians should not be determined by race/color categories. Native Americans (0.4% of the Brazilian population), virtually absent from the study cohorts, display wide interethnic diversity in frequency of some tier 1 variants (eg, NUDT15∗3 and TPMT∗3A) and/or differ markedly from non-Indigenous people in frequency of some variant alleles (eg, CYP2C19∗17). Collectively, the data support the notion that population diversity must be taken into account on the design and implementation of pharmacogenetic testing panels.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043166","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

Association of Mitochondrial DNA Copy Number in Peripheral Blood with Risk and Prognosis in Acute Aortic Syndrome.

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-01-23 DOI: 10.1016/j.jmoldx.2024.12.009

Chun Yin, Ying Wang, Hao Yang, Gaoshan Li, Zhichun Gao, Kunyan Li, Guiquan Zhou, Xuan Zhang, Xiangzheng Xu, Hu Tan, Jun Jin

{"title":"Association of Mitochondrial DNA Copy Number in Peripheral Blood with Risk and Prognosis in Acute Aortic Syndrome.","authors":"Chun Yin, Ying Wang, Hao Yang, Gaoshan Li, Zhichun Gao, Kunyan Li, Guiquan Zhou, Xuan Zhang, Xiangzheng Xu, Hu Tan, Jun Jin","doi":"10.1016/j.jmoldx.2024.12.009","DOIUrl":"10.1016/j.jmoldx.2024.12.009","url":null,"abstract":"<p><p>Previous studies have reported that mitochondrial DNA copy number (mtDNA-CN) of blood was associated with a series of aging-related diseases. However, it remains unknown whether mtDNA-CN can be a potential biomarker of acute aortic syndromes (AASs). The mtDNA-CN in blood of 190 male patients with AAS and 207 healthy controls were detected by standardized real-time quantitative PCR-based assay. The mtDNA sequencing data of blood and myocardial muscle in 134 individuals were used to analyze mtDNA somatic mutations in blood. mtDNA-CN in peripheral blood was negatively correlated with age of individuals. Further analysis based on next-generation sequencing data demonstrated numbers and heteroplasmy of mtDNA mutations were positively correlated with age. Remarkably, mtDNA-CN of patients with AAS was lower than that of healthy controls. Logistic regression also showed that mtDNA-CN was independently associated with risk of AAS. During follow-up, patients with the lowest mtDNA-CN quartile had a hazard ratio of 2.543 for all-cause-mortality and 1.964 for composite end points compared with the other patients. Moreover, multivariate Cox regression indicated that lowest mtDNA-CN quartile was independently associated with all-cause mortality in patients with AAS. Our study demonstrated a negative correlation between mtDNA-CN and age. Moreover, lower mtDNA-CN in peripheral blood was significantly associated with higher risk and worse prognosis of AAS. It provided crucial evidence supporting the potential of mtDNA-CN as a novel biomarker of AAS.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043157","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