Journal of Molecular Diagnostics最新文献

{"title":"Reviewer Acknowledgment","authors":"","doi":"10.1016/j.jmoldx.2024.01.001","DOIUrl":"https://doi.org/10.1016/j.jmoldx.2024.01.001","url":null,"abstract":"","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 3","pages":"Pages 228-229"},"PeriodicalIF":4.1,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139907486","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}

{"title":"Microarray-Based DNA Methylation Profiling","authors":"Marco L. Leung ,&nbsp;Zied Abdullaev ,&nbsp;Lucas Santana-Santos ,&nbsp;John M. Skaugen ,&nbsp;Stephen Moore ,&nbsp;Jianling Ji","doi":"10.1016/j.jmoldx.2024.02.001","DOIUrl":"10.1016/j.jmoldx.2024.02.001","url":null,"abstract":"<div><p>Microarray-based methylation profiling has emerged as a valuable tool for refining diagnoses and revealing novel tumor subtypes, particularly in central nervous system tumors. Despite the increasing adoption of this technique in clinical genomic laboratories, no technical standards have been published in establishing minimum criteria for test validation. A working group with experience and expertise in DNA-based methylation profiling tests on central nervous system tumors collaborated to develop practical discussion points and focus on important considerations for validating this test in clinical laboratory settings. The experience in validating this methodology in a clinical setting is summarized. Specifically, the advantages and challenges associated with utilizing an in-house classifier compared with a third-party classifier are highlighted. Additionally, experiences in demonstrating the assay's sensitivity and specificity, establishing minimum sample criteria, and implementing quality control metrics are described. As methylation profiling for tumor classification expands to other tumor types and continues to evolve for various other applications, the critical considerations described here are expected to serve as a guidance for future efforts in establishing professional guidelines for this assay.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 6","pages":"Pages 447-455"},"PeriodicalIF":4.1,"publicationDate":"2024-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824000345/pdfft?md5=060c0469b7baac195e16471504bacd2f&pid=1-s2.0-S1525157824000345-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913937","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}

{"title":"Analytical Validation of a 37-Gene Next-Generation Sequencing Panel for Myeloid Malignancies and Review of Initial Findings Incorporating Updated 2022 Diagnostic and Prognostic Guidelines","authors":"Becky Leung ,&nbsp;Hnin Aung ,&nbsp;Adayapalam Nandini ,&nbsp;Ghusoon Abdulrasool ,&nbsp;Chiyan Lau ,&nbsp;Louise Seymour","doi":"10.1016/j.jmoldx.2024.01.010","DOIUrl":"10.1016/j.jmoldx.2024.01.010","url":null,"abstract":"<div><p>Myeloid neoplasms are clonal disorders that arise via acquisition of genetic mutations leading to excessive proliferation and defective differentiation. Mutational profiling is vital as it has implications for diagnosis, prognosis, and therapeutic decision-making. Next-generation sequencing (NGS) has become a mainstay in the evaluation of myeloid malignancies, as it enables efficient characterization of multiple genetic changes. Herein, the analytical validation of the 37-gene Archer VariantPlex Core Myeloid panel is reported, using 58 DNA specimens with 87 single-nucleotide variants and 23 insertions/deletions. The panel achieved good depth of coverage, 100% analytical sensitivity and specificity for single-nucleotide variants and insertions/deletions ≤21 bp, and 100% reproducibility, with a reportable limit of detection determined as 5%. The Archer NGS panel can accurately and reproducibly detect variants of clinical significance in myeloid neoplasms. A retrospective analysis of 535 clinical specimens tested with the Archer NGS panel showed a frequency and pattern of mutations across myeloid malignancies that were similar to other published studies. A review of the diagnostic classification of patients with acute myeloid leukemia and myelodysplastic syndrome using the World Health Organization 2017/2022 and International Consensus Classification 2022 guidelines, in addition to European LeukemiaNet 2017/2022 risk stratification of patients with acute myeloid leukemia, was also performed to assess the utility of the molecular information provided by the Archer NGS panel.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 5","pages":"Pages 399-412"},"PeriodicalIF":4.1,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139888383","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}

{"title":"Significance Associated with Phenotype Score Aids in Variant Prioritization for Exome Sequencing Analysis","authors":"Brian Lee ,&nbsp;Lily Nasanovsky ,&nbsp;Lishuang Shen ,&nbsp;Dennis T. Maglinte ,&nbsp;Yachen Pan ,&nbsp;Xiaowu Gai ,&nbsp;Ryan J. Schmidt ,&nbsp;Gordana Raca ,&nbsp;Jaclyn A. Biegel ,&nbsp;Megan Roytman ,&nbsp;Paul An ,&nbsp;Carol J. Saunders ,&nbsp;Emily G. Farrow ,&nbsp;Soheil Shams ,&nbsp;Jianling Ji","doi":"10.1016/j.jmoldx.2024.01.009","DOIUrl":"10.1016/j.jmoldx.2024.01.009","url":null,"abstract":"<div><p>Several <em>in silico</em> annotation-based methods have been developed to prioritize variants in exome sequencing analysis. This study introduced a novel metric Significance Associated with Phenotypes (SAP) score, which generates a statistical score by comparing an individual's observed phenotypes against existing gene–phenotype associations. To evaluate the SAP score, a retrospective analysis was performed on 219 exomes. Among them, 82 family-based and 35 singleton exomes had at least one disease-causing variant that explained the patient's clinical features. SAP scores were calculated, and the rank of the disease-causing variant was compared with a known method, Exomiser. Using the SAP score, the known causative variant was ranked in the top 10 retained variants for 94% (77 of 82) of the family-based exomes and in first place for 73% of these cases. For singleton exomes, the SAP score analysis ranked the known pathogenic variants within the top 10 for 80% (28 of 35) of cases. The SAP score, which is independent of detected variants, demonstrates comparable performance with Exomiser, which considers both phenotype and variant-level evidence simultaneously. Among 102 cases with negative results or variants of uncertain significance, SAP score analysis revealed two cases with a potential new diagnosis based on rank. The SAP score, a phenotypic quantitative metric, can be used in conjunction with standard variant filtration and annotation to enhance variant prioritization in exome analysis.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 5","pages":"Pages 337-348"},"PeriodicalIF":4.1,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742568","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}

{"title":"Comprehensive Genomic Analysis Identifies a Diverse Landscape of Sideroblastic and Nonsideroblastic Iron-Related Anemias with Novel and Pathogenic Variants in an Iron-Deficient Endemic Setting","authors":"Pankaj Sharma ,&nbsp;Prateek Bhatia ,&nbsp;Minu Singh ,&nbsp;Manu Jamwal ,&nbsp;Swetha Pallavelangini ,&nbsp;Reena Das ,&nbsp;Pankaj Malhotra ,&nbsp;Savita V. Attri ,&nbsp;Sarah Ducamp ,&nbsp;Mark D. Fleming ,&nbsp;Amita Trehan","doi":"10.1016/j.jmoldx.2024.01.011","DOIUrl":"10.1016/j.jmoldx.2024.01.011","url":null,"abstract":"<div><p>Inherited iron metabolism defects are possibly missed or underdiagnosed in iron-deficient endemic settings because of a lack of awareness or a methodical screening approach. Hence, we systematically evaluated anemia cases (2019 to 2021) based on clinical phenotype, normal screening tests (high-performance liquid chromatography, α gene sequencing, erythrocyte sedimentation rate, C-reactive protein, and tissue transglutaminase), and abnormal iron profile by targeted next-generation sequencing (26-gene panel) supplemented with whole-exome sequencing, multiplex ligation probe amplification/mitochondrial DNA sequencing, and chromosomal microarray. Novel variants in <em>ALAS2</em>, <em>STEAP3</em>, and <em>HSPA9</em> genes were functionally validated. A total of 290 anemia cases were screened, and 41 (14%) enrolled for genomic testing as per inclusion criteria. Comprehensive genomic testing revealed pathogenic variants in 23 of 41 cases (56%). Congenital sideroblastic anemia was the most common diagnosis (14/23; 61%), with pathogenic variations in <em>ALAS2</em> (<em>n</em> = 6), <em>SLC25A38</em> (<em>n</em> = 3), <em>HSPA9</em> (<em>n</em> = 2) and <em>HSCB</em>, <em>SLC19A2</em>, and mitochondrial DNA deletion (<em>n</em> = 1 each). Nonsideroblastic iron defects included <em>STEAP3</em>-related microcytic anemia (2/23; 8.7%) and hypotransferrenemia (1/23; 4.3%). A total of 6 of 22 cases (27%) revealed a non-iron metabolism gene defect on whole-exome sequencing. Eleven novel variants (including variants of uncertain significance) were noted in 13 cases. Genotype-phenotype correlation revealed a significant association of frameshift/nonsense/splice variants with lower presentation age (0.8 months versus 9 years; <em>P</em> &lt; 0.01) compared with missense variants. The systematic evaluation helped uncover an inherited iron defect in 41% (17/41) of cases, suggesting the need for active screening and awareness for these rare diseases in an iron-deficient endemic population.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 5","pages":"Pages 430-444"},"PeriodicalIF":4.1,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S152515782400031X/pdfft?md5=1ae4b2da1ba4eebc15884dfa8d76ec2e&pid=1-s2.0-S152515782400031X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742546","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}

{"title":"Enhancing Trypanosomatid Identification and Genotyping with Oxford Nanopore Sequencing","authors":"Lissa Cruz-Saavedra ,&nbsp;Carlos Ospina ,&nbsp;Luz H. Patiño ,&nbsp;Juan C. Villar ,&nbsp;Luis D. Sáenz Pérez ,&nbsp;Omar Cantillo-Barraza ,&nbsp;Jeiczon Jaimes-Dueñez ,&nbsp;Nathalia Ballesteros ,&nbsp;Tatiana Cáceres ,&nbsp;Gustavo Vallejo ,&nbsp;Juan D. Ramírez","doi":"10.1016/j.jmoldx.2024.01.012","DOIUrl":"10.1016/j.jmoldx.2024.01.012","url":null,"abstract":"<div><p>Trypanosomatids, including <em>Trypanosoma</em> and <em>Leishmania</em> species, present significant medical and veterinary challenges, causing substantial economic losses, health complications, and even fatalities. Diagnosing and genotyping these species and their genotypes is often complex, involving multiple steps. This study aimed to develop an amplicon-based sequencing (ABS) method using Oxford Nanopore long-read sequencing to enhance Trypanosomatid detection and genotyping. The <em>18S</em> rDNA gene was targeted for its inter-species conservation. The Trypanosomatid-ABS method effectively distinguished between 11 <em>Trypanosoma</em> species (including <em>Trypanosoma evansi</em>, <em>Trypanosoma theileri</em>, <em>Trypanosoma vivax</em>, and <em>Trypanosoma rangeli</em>) and 6 <em>Trypanosoma cruzi</em> discrete typing units (TcI to TcVI and TcBat), showing strong concordance with conventional methods (κ index of 0.729, <em>P</em> &lt; 0.001). It detected co-infections between Trypanosomatid genera and <em>T. cruzi</em>, with a limit of detection of one parasite per mL. The method was successfully applied to human, animal, and triatomine samples. Notably, TcI predominated in chronic Chagas samples, whereas TcII and TcIV were found in the acute stage. Triatomine vectors exhibited diverse Trypanosomatid infections, with <em>Triatoma dimidiata</em> mainly infected with TcI and occasional TcBat co-infections, and <em>Rhodnius prolixus</em> showing TcI and TcII infections, along with <em>T. rangeli</em> co-infections and mixed TcII infections. Animals were infected with <em>T. vivax, T. theileri</em>, and <em>T. evansi</em>. The ABS method's high resolution, sensitivity, and accuracy make it a valuable tool for understanding Trypanosomatid dynamics, enhancing disease control strategies, and enabling targeted interventions.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 5","pages":"Pages 323-336"},"PeriodicalIF":4.1,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824000321/pdfft?md5=a36b971c908fdd97f86908f9c7247a7d&pid=1-s2.0-S1525157824000321-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742567","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}

{"title":"Extraction of Cell-Free DNA","authors":"Simone K. Terp ,&nbsp;Inge S. Pedersen ,&nbsp;Malene P. Stoico","doi":"10.1016/j.jmoldx.2024.01.008","DOIUrl":"10.1016/j.jmoldx.2024.01.008","url":null,"abstract":"<div><p>Cell-free DNA (cfDNA) serves as a valuable biomarker for early disease detection and monitoring. However, the use of cfDNA for analysis faces challenges owing to general low but variable abundance and fragmentation. Preanalytical factors, including cfDNA extraction, impact cfDNA quality and quantity. Efficient and robust cfDNA extraction is essential for reliable results in downstream applications, and various commercial extraction methods exist, each with trade-offs. To aid researchers and clinicians in choosing the proper cfDNA extraction method, manual, semiautomated, and automated methods were evaluated, including the QIAamp Circulating Nucleic Acid Kit (manual and QIAcube), QIAamp MinElute ccfDNA Kit (QIAcube), and QIAsymphony DSP Circulating DNA Kit (QIAsymphony). For each extraction method, cfDNA was extracted on two separate days, using samples obtained from 18 healthy donors. This study assessed extraction efficiency, quantity, and quality using droplet digital PCR and TapeStation. The QIAamp Circulating Nucleic Acid Kit, both manual and semiautomated, outperformed the QIAamp MinElute ccfDNA Kit (QIAcube) and QIAsymphony DSP Circulating DNA Kit (QIAsymphony), showing higher recovery rates and cfDNA quantity. All methods were reproducible, with no day-to-day variability and no contamination by high-molecular-weight DNA. The QIAamp Circulating Nucleic Acid Kit offers high yield without compromising quality. Implementation of the method should consider specific study and clinical needs, taking into account each method's advantages and limitations for optimal outcomes.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 4","pages":"Pages 310-319"},"PeriodicalIF":4.1,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S152515782400014X/pdfft?md5=30cbd9c79072993ea112539e0f69027b&pid=1-s2.0-S152515782400014X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669326","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}

{"title":"Enhancing the Reliability of PMP22 Copy Number Variation Detection with an Inherited Peripheral Neuropathy Panel","authors":"Jong Kwon Lee ,&nbsp;Hyemi Kwon ,&nbsp;Jong-Ho Park ,&nbsp;Mi-Ae Jang ,&nbsp;Young-gon Kim ,&nbsp;Jong-Won Kim ,&nbsp;Byung-Ok Choi ,&nbsp;Ja-Hyun Jang","doi":"10.1016/j.jmoldx.2024.01.004","DOIUrl":"10.1016/j.jmoldx.2024.01.004","url":null,"abstract":"<div><p>The utility of the next-generation sequencing (NGS) panel could be increased in hereditary peripheral neuropathies, given that the duplication of <em>PMP22</em> is a major abnormality. In the present study, the analytical performance of an algorithm for detecting <em>PMP22</em> copy number variation (CNV) from the NGS panel data was evaluated. The NGS panel covers 141 genes, including <em>PMP22</em> and five genes within 1.5-megabase duplicated region at 17p11.2. CNV calling was performed using a laboratory-developed algorithm. Among the 92 cases subjected to targeted NGS panel from March 2018 to January 2021, 26 were suggestive of <em>PMP22</em> CNV. Multiplex ligation-dependent probe amplification analysis was performed in 58 cases, and the results were 100% concordant with the NGS data (23 duplications, 2 deletions, and 33 negatives). Analytical performance of the pipeline was further validated by another blind data set, including 14 positive and 20 negative samples. Reliable detection of <em>PMP22</em> CNV was possible by analyzing not only <em>PMP22</em> but also the adjacent genes within the 1.5-megabase region of 17p11.2. On the basis of the high accuracy of CNV calling for <em>PMP22</em>, the testing strategy for diagnosis of peripheral polyneuropathies could be simplified by reducing the need for multiplex ligation-dependent probe amplification.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 4","pages":"Pages 304-309"},"PeriodicalIF":4.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824000102/pdfft?md5=0f6bba51e52c8135d0b574cc864f902e&pid=1-s2.0-S1525157824000102-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669073","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}

{"title":"The Clinical Validity of Urinary Pellet DNA Monitoring for the Diagnosis of Recurrent Bladder Cancer","authors":"Masakazu Abe ,&nbsp;Hayato Hiraki ,&nbsp;Takashi Tsuyukubo ,&nbsp;Sadahide Ono ,&nbsp;Shigekatsu Maekawa ,&nbsp;Daichi Tamura ,&nbsp;Akiko Yashima-Abo ,&nbsp;Renpei Kato ,&nbsp;Hiromitsu Fujisawa ,&nbsp;Takeshi Iwaya ,&nbsp;Woong-Yang Park ,&nbsp;Masashi Idogawa ,&nbsp;Takashi Tokino ,&nbsp;Wataru Obara ,&nbsp;Satoshi S. Nishizuka","doi":"10.1016/j.jmoldx.2024.01.006","DOIUrl":"10.1016/j.jmoldx.2024.01.006","url":null,"abstract":"<div><p>The aim of this study was to evaluate the clinical validity of monitoring urine pellet DNA (upDNA) of bladder cancer (BC) by digital PCR (dPCR) as a biomarker for early recurrence prediction, treatment efficacy evaluation, and no-recurrence corroboration. Tumor panel sequencing was first performed to select patient-unique somatic mutations to monitor both upDNA and circulating tumor DNA (ctDNA) by dPCR. For longitudinal monitoring using upDNA as well as plasma ctDNA, an average of 7.2 (range, 2 to 12) time points per case were performed with the dPCR assay for 32 previously treated and untreated patients with BC. Clinical recurrence based on imaging and urine cytology was compared using upDNA variant allele frequency (VAF) dynamics. A continuous increasing trend of upDNA VAF ≥1% was considered to indicate molecular recurrence. Most (30/32; 93.8%) cases showed at least one traceable somatic mutation. In 5 of 7 cases (71.4%) with clinical recurrence, upDNA VAF &gt;1% was detected 7 to 15 months earlier than the imaging diagnosis. The upDNA VAF remained high after initial treatment for locally recurrent cases. The clinical validity of upDNA monitoring was confirmed with the observation that 26 of 30 cases (86.7%) were traceable. Local recurrences were not indicated by ctDNA alone. The results support the clinical validity of upDNA monitoring in the management of recurrent BC.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 4","pages":"Pages 278-291"},"PeriodicalIF":4.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824000126/pdfft?md5=290b2b6f6302a928cb57d43916060d40&pid=1-s2.0-S1525157824000126-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668939","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}

{"title":"Next-Generation Sequencing Trends among Adult Patients with Select Advanced Tumor Types","authors":"Andrea Ferreira-Gonzalez ,&nbsp;Brian Hocum ,&nbsp;Gilbert Ko ,&nbsp;Sohul Shuvo ,&nbsp;Sreevalsa Appukkuttan ,&nbsp;Svetlana Babajanyan","doi":"10.1016/j.jmoldx.2024.01.005","DOIUrl":"10.1016/j.jmoldx.2024.01.005","url":null,"abstract":"<div><p>There are limited data on the prevalence of next-generation sequencing (NGS) in the United States, especially in light of the increasing importance of identifying actionable oncogenic variants due to molecular biomarker–based therapy approvals. This retrospective study of adult patients with select metastatic solid tumors and central nervous system tumors from the Optum Clinformatics Data Mart US health care claims database (January 1, 2014, to June 30, 2021; <em>N</em> = 63,209) examined NGS use trends over time. A modest increase in NGS was observed across tumor types from 2015 (0.0% to 1.5%) to 2021 (2.1% to 17.4%). A similar increase in NGS rates was also observed across key periods; however, rates in the final key period remained &lt;10% for patients with breast, colorectal, head and neck, soft tissue sarcoma, and thyroid cancers, as well as central nervous system tumors. The median time to NGS from diagnosis was shortest among patients with non–small-cell lung cancer and longest for patients with breast cancer. Predictors of NGS varied by tumor type; test rates for minorities in select tumor types appeared comparable to the White population. Despite improving payer policies to expand coverage of NGS and molecular biomarker–based therapy approvals, NGS rates remained low across tumor types. Given the potential for improved patient outcomes with molecular biomarker–based therapy, further efforts to improve NGS rates are warranted.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 4","pages":"Pages 292-303"},"PeriodicalIF":4.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824000114/pdfft?md5=f6bc1fb11cec3cd2e9b7bcb8752465d9&pid=1-s2.0-S1525157824000114-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669076","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}