Molecular Diagnosis & Therapy最新文献

{"title":"Molecular Therapeutics in Development to Treat Hyperlipoproteinemia.","authors":"Maud Ahmad, Robert A Hegele","doi":"10.1007/s40291-024-00768-0","DOIUrl":"10.1007/s40291-024-00768-0","url":null,"abstract":"<p><p>Clinical endpoints caused by hyperlipoproteinemia include atherosclerotic cardiovascular disease and acute pancreatitis. Emerging lipid-lowering therapies targeting proprotein convertase subtilisin/kexin 9 (PCSK9), lipoprotein(a), apolipoprotein C-III, and angiopoietin-like protein 3 represent promising advances in the management of patients with hyperlipoproteinemia. These therapies offer novel approaches for lowering pathogenic lipid and lipoprotein species, particularly in patients with serious perturbations who are not adequately controlled with conventional treatments or who are unable to tolerate them. Molecular targets for these novel therapeutic agents were identified and validated through genetic epidemiology studies. Proprotein convertase subtilisin/kexin 9 inhibitors (e.g., monoclonal antibodies and small interfering RNA) have revolutionized hypercholesterolemia management by significantly reducing both low-density lipoprotein cholesterol levels and major cardiovascular events. Genome editing of PCSK9 promises to provide a potential cure for patients with familial hypercholesterolemia. Several investigational lipoprotein(a)-targeting therapies aim to reduce the risk of atherosclerotic cardiovascular disease and aortic valve disease, although definitive clinical endpoint studies remain to be completed. Inhibition of APOC3 messenger RNA expression by olezarsen and plozasiran significantly lowers plasma triglyceride levels and markedly reduces pancreatitis risk in patients with familial chylomicronemia syndrome. Finally, angiopoietin-like protein 3 inhibition by the monoclonal antibody evinacumab has transformed management of patients with homozygous familial hypercholesterolemia. Together, these novel agents expand the therapeutic cache, offering personalized lipid-lowering strategies for high-risk patients with hyperlipoproteinemia, improving clinical outcomes and addressing previously unmet medical needs.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"291-305"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061448","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":"Cell-Free DNA: Features and Attributes Shaping the Next Frontier in Liquid Biopsy.","authors":"Neeti Swarup, Ho Yeung Leung, Irene Choi, Mohammad Arshad Aziz, Jordan C Cheng, David T W Wong","doi":"10.1007/s40291-025-00773-x","DOIUrl":"https://doi.org/10.1007/s40291-025-00773-x","url":null,"abstract":"<p><p>Cell-free DNA (cfDNA) is changing the face of liquid biopsy as a minimally invasive tool for disease detection and monitoring, with its main applications in oncology and prenatal testing, and rising roles in transplant patient monitoring. However, the processes of cfDNA biogenesis, fragmentation, and clearance are complex and require further investigation. Evidence suggests that cfDNA production relates to mechanisms of cell death and DNA repair, both of which further influence fragment size and its applicability as a biomarker. An emerging domain, cfDNA fragmentomics is being explored for advancing the field of diagnostics using non-mutational signatures such as fragment size ratios and methylation patterns. Thus, this review examines structural diversity in cfDNA with various fragment sizes. In examining these cfDNA subsets, we discuss their distinct biological origins and potential clinical utility. Development of sequencing methodologies has broadened the application of cfDNA in diagnosing cancers and organ-specific pathologies, as well as directing personalized therapies. This has been achieved by identifying and uncovering different subsets of cfDNA in biofluids using different methodologies and biofluids. Different cfDNA subsets provide important insights regarding genomic and epigenetic features, enhancing the understanding of gene regulation, tissue-specific functions, and disease progression. Advancement of these key areas further asserts increasing clinical relevance for the use of cfDNA as a biomarker. Continued exploration of cfDNA subsets is expected to drive further innovation in liquid biopsy and its integration into routine clinical practice.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"29 3","pages":"277-290"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051863","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":"Flavonoids in the Treatment of Non-small Cell Lung Cancer via Immunomodulation: Progress to Date.","authors":"Man-Shan Liang, Yang Huang, Sheng-Feng Huang, Qi Zhao, Zhe-Sheng Chen, Shuo Yang","doi":"10.1007/s40291-025-00772-y","DOIUrl":"10.1007/s40291-025-00772-y","url":null,"abstract":"<p><p>Lung cancer is one of the most common malignancies in the world, while non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. Most patients with NSCLC have advanced stage disease at diagnosis, and the 5-year survival rate can be discouragingly low. Flavonoids are widely found in fruits, vegetables, teas, and medicinal plants, with a variety of functional effects, including anti-inflammatory, antioxidant, and anticancer properties. This review aims to focus on the research progress of flavonoids in the treatment of NSCLC, including immunomodulatory effects on NSCLC, promotion of reactive oxygen species (ROS) production, interaction with microRNA (miRNA), and interactions with certain proteins. In addition, combining flavonoids and anticancer agents, radiotherapy, or nanoparticles can reverse NSCLC  drug resistance, inducing apoptosis of cancer cells. It therefore appears that flavonoids alone or in combination with other treatment agents may be a promising therapeutic modality for treating NSCLC, with great potential in mass production and clinical applications.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"307-327"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544175","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":"Clinical Validation of a Targeted RNA-Sequencing Assay for Driver Gene Alteration Detection in Non-Small Cell Lung Cancer.","authors":"Ji Li, Xiaohua Shi, Hui Zhang, Xiaojing Lin, Shan Zheng, Weizhi Chen, Yang Zhou, Zhiyong Liang","doi":"10.1007/s40291-025-00774-w","DOIUrl":"10.1007/s40291-025-00774-w","url":null,"abstract":"<p><strong>Background and objective: </strong>With the increasing number of diagnostic biomarkers associated with tumor diagnosis, targeted therapy, and immunotherapy, access to clinical pathological specimens of an appropriate size for analysis is becoming a problem. Conventional high-throughput sequencing assays for non-small cell lung cancer (NSCLC) often necessitate the extraction of separate DNA and RNA samples to achieve precise detection of various mutation types. This study aimed to employ RNA-next-generation sequencing (NGS) technology to simultaneously detect different types of mutations in NSCLC samples, including single nucleotide variations, insertions and deletions, fusions/rearrangements, and exon skipping, thereby addressing the issue of limited sample availability.</p><p><strong>Methods: </strong>Two hundred and twenty cases of formalin-fixed paraffin-embedded NSCLC clinical specimens were retrospectively included for targeted RNA sequencing based on the principle of probe hybridization capture. Lung cancer tissue samples with different storage times were compared for success in DNA-NGS and RNA-NGS assays. The clinical detection performance of RNA-NGS was evaluated by comparing its results to those of DNA-NGS and clinical assays. Samples with inconsistent results were further verified by immunohistochemistry, amplification refractory mutation system-polymerase chain reaction, or droplet digital polymerase chain reaction.</p><p><strong>Results: </strong>DNA-NGS exhibited an overall success rate of 91.82% in all samples, while RNA-NGS achieved an overall success rate of 92.73%. However, the success rate declined with longer storage times. Compared with DNA-NGS, targeted RNA sequencing for single nucleotide variation/insertion and deletion detection achieved a sensitivity of 93.75%, a specificity of 100%, and an overall concordance of 97.86%. Compared with the validated results, it achieved a sensitivity of 97.96%, a specificity of 99.28%, an and overall concordance of 98.93% in fusion/rearrangement and Met exon skipping detection, which was superior to DNA-NGS. Compared to clinical testing, this assay demonstrated a sensitivity of 93.33%, a specificity of 100%, and an overall concordance rate of 97.93%.</p><p><strong>Conclusions: </strong>This study substantiates that the targeted RNA-sequencing assay, based on probe hybridization capture, represents a superior detection technology platform for the application of drug targeting. It expeditiously and reliably provides all the requisite biomarkers for current NSCLC targeted therapies in a single-sample testing workflow, facilitating rapid clinical diagnosis and the formulation of rational treatment plans by clinicians.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"381-391"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634894","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":"Psoriasis: A Multidimensional Review of Onset, Progression, Treatment, and the Evolution of Disease Models.","authors":"Yanhong Pan, Jueyao Zou, Tongyao Hu, Ziyan Zhu, Zhengyu Zhang, Wenxing Chen, Yin Lu","doi":"10.1007/s40291-025-00776-8","DOIUrl":"10.1007/s40291-025-00776-8","url":null,"abstract":"<p><p>Psoriasis is a widespread chronic inflammatory skin disease. Recent advances in the molecular mechanisms of psoriasis have unveiled numerous potential therapeutic targets. However, the complex nature of psoriasis, coupled with the limitations of current research methodologies, diagnostic techniques, and gaps in knowledge, contributes to the variability in treatment efficacy among patients, recurrence following drug cessation, and therapeutic failures. Emerging technologies, including artificial intelligence, multi-omics approaches, novel modeling systems such as skin organoids, and precision medicine, are being explored to address these challenges. This review explores the latest findings in genetics, cytology, microbiology, metabolism, and molecular biology related to psoriasis pathogenesis, development, and recurrence to improve the understanding of psoriasis and find new therapeutic directions and targets. It updates the psoriasis models, diagnostic methods, and treatment while comparing their characteristics and limitations. It also provides new biomarkers and indicators to assist diagnosis and treatment. Along with traditional drugs, it explores emerging targeted drugs, cell therapies, nutrition management, microbial therapy, and traditional Chinese medicine in advancing personalized, precision medicine for psoriasis.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"345-366"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755553","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":"Effective Utilization of a Customized Targeted Hybrid Capture RNA Sequencing in the Routine Molecular Categorization of Adolescent and Adult B-Lineage Acute Lymphoblastic Leukemia: A Real-World Experience.","authors":"Sreejesh Sreedharanunni, Venus Thakur, Anand Balakrishnan, Man Updesh Singh Sachdeva, Prabhjot Kaur, Sudhanshi Raina, Manu Jamwal, Charanpreet Singh, Praveen Sharma, Nabhajit Mallik, Shano Naseem, Pulkit Rastogi, Arihant Jain, Gaurav Prakash, Alka Khadwal, Pankaj Malhotra, Reena Das","doi":"10.1007/s40291-025-00779-5","DOIUrl":"10.1007/s40291-025-00779-5","url":null,"abstract":"<p><strong>Introduction: </strong>Recent World Health Organization (WHO) and International Consensus Classifications have introduced numerous molecular entities in B-lineage acute lymphoblastic leukemia (B-ALL), necessitating comprehensive genomic characterization by detecting gene fusions, expression, mutations, and exon deletions. While whole-genome plus transcriptome sequencing is the ideal strategy, it remains cost-prohibitive for routine use. This study reports a cost-effective and reasonably efficient alternate approach integrating a customized targeted hybrid capture RNA sequencing (RNAseq) into the routine workup.</p><p><strong>Methodology: </strong>A total of 95 consecutive adolescent/adult B-ALL cases negative for common chimeric gene fusions (CGF) (BCR::ABL1, KMT2A::AFF1, TCF3::PBX1, and ETV6::RUNX1) were analyzed using a customized 69-gene targeted RNAseq panel. In total, three fusion detection pipelines, the Trinity Cancer Transcriptome Analysis Toolkit (CTAT) Mutations pipeline, and the Toblerone alignment tool were employed, and the results were compared with fluorescence in situ hybridization (FISH)/multiplex ligation-dependent probe amplification (MLPA) testing.</p><p><strong>Results: </strong>RNAseq identified fusions in 43% of cases (including BCR::ABL1-like: 15.8% and IGH::DUX4: 10.5%), demonstrating superior detection of cryptic intrachromosomal rearrangements. Somatic variants were detected in 30% of cases (including rat sarcoma (RAS) pathway and Janus kinase (JAK)-signal transducers and activators of transcription (STAT) variants in 18% and 5.3% respectively), and IKZF1 deletions were detected in 25% (77% concordance with MLPA). The integration of targeted RNAseq and comprehensive bioinformatic analysis with flow-cytometry-based ploidy analysis and FISH-based IGH rearrangements helped categorize 79% of common CGF-negative B-ALL. The BCR::ABL1/BCR::ABL1-like group showed a higher frequency of pathogenic IKZF1 deletions (50% versus 21.7%; p = 0.011), measurable residual disease (92% versus 51%; p = 0.009), and poorer overall survival (8.6 versus 22.8 months; p = 0.07).</p><p><strong>Discussion and conclusions: </strong>Effective utilization of RNAseq data by comprehensive bioinformatic analysis to test fusions, mutations, and deletions, supported by only minimal supplementary FISH testing, provides a practical, cost-effective solution for the molecular characterization of B-ALL in real-world scenarios until a single alternative and cost-effective test is available.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"407-418"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789369","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":"Selecting Targets for Molecular Imaging of Gastric Cancer: An Immunohistochemical Evaluation.","authors":"Ruben D Houvast, Maurice van Duijvenvoorde, Kira Thijse, Wobbe O de Steur, Lioe-Fee de Geus-Oei, A Stijn L P Crobach, Jacobus Burggraaf, Alexander L Vahrmeijer, Peter J K Kuppen","doi":"10.1007/s40291-024-00755-5","DOIUrl":"10.1007/s40291-024-00755-5","url":null,"abstract":"<p><strong>Purpose: </strong>Tumor-targeted positron emission tomography (PET) and fluorescence-guided surgery (FGS) could address current challenges in pre- and intraoperative imaging of gastric cancer. Adequate selection of molecular imaging targets remains crucial for successful tumor visualization. This study evaluated the potential of integrin α_vβ₆, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM) and human epidermal growth factor receptor-2 (HER2) for molecular imaging of primary gastric cancer, as well as lymph node and distant metastases.</p><p><strong>Methods: </strong>Expression of α_vβ₆, CEACAM5, EGFR, EpCAM and HER2 was determined using immunohistochemistry in human tissue specimens of primary gastric adenocarcinoma, healthy surrounding stomach, esophageal and duodenal tissue, tumor-positive and tumor-negative lymph nodes, and distant metastases, followed by quantification using the total immunostaining score (TIS).</p><p><strong>Results: </strong>Positive biomarker expression in primary gastric tumors was observed in 86% for α_vβ₆, 72% for CEACAM5, 77% for EGFR, 93% for EpCAM and 71% for HER2. Tumor expression of CEACAM5, EGFR and EpCAM was higher compared to healthy stomach tissue expression, while this was not the case for α_vβ₆ and HER2. Tumor-positive lymph nodes could be distinguished from tumor-negative lymph nodes, with accuracy ranging from 82 to 93% between biomarkers. CEACAM5, EGFR and EpCAM were abundantly expressed on distant metastases, with expression in 88-95% of tissue specimens.</p><p><strong>Conclusion: </strong>Our findings show that CEACAM5, EGFR and EpCAM are promising targets for molecular imaging of primary gastric cancer, as well as visualization of both lymph node and distant metastases. Further clinical evaluation of PET and FGS tracers targeting these antigens is warranted.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"213-227"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631431","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":"A miRNA-Based Approach in Autosomal Dominant Polycystic Kidney Disease: Challenges and Insights from Adult to Pediatric Evidence.","authors":"Caterina Vitulano, Gianmario Forcina, Simone Colosimo, Vittoria Frattolillo, Annalisa Valentina Villani, Pierluigi Marzuillo, Emanuele Miraglia Del Giudice, Anna Di Sessa","doi":"10.1007/s40291-024-00761-7","DOIUrl":"10.1007/s40291-024-00761-7","url":null,"abstract":"<p><p>Autosomal dominant polycystic kidney disease (ADPKD) represents the most common inherited kidney disorder leading to kidney failure in a significant percentage of patients over time. Although previously considered as an adult disease, robust evidence demonstrated that clinical manifestations might occur during childhood and adolescence. Therefore, early identification and treatment of the disease are of cardinal importance for pediatricians to ensure the best long-term outcomes. To date, licensed treatment options are limited but promising potential therapeutic targets are emerging. Among these, an intriguing pathophysiological role for microRNAs as small molecules with a critical role in regulating gene expression has been considered possible in ADPKD. Indeed, numerous circulating microRNAs have been found to be dysregulated in ADPKD, suggesting their potential role as biomarkers and therapeutic targets. Based on this background, further detailed insights into the mechanisms of miRNAs contributing to ADPKD development might pave the way for their effective application as a targeted treatment in young patients with ADPKD. We aimed to summarize the most recent evidence in this fascinating research area, providing a comprehensive overview of the current landscape of specific microRNAs in ADPKD as a potential innovative therapeutic strategy for these young patients.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"183-193"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014874","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":"Development of a New Rapid Simultaneous Molecular Assay for the Detection of STI Pathogens and Drug Resistance-Associated Mutations.","authors":"Masashi Michibuchi, Takafumi Yoshikane, Yuma Matsuba, Tomomi Yamazaki, Shinji Hatakeyama, Masaki Takanashi, Takehiro Oikawa, Hiromichi Suzuki","doi":"10.1007/s40291-024-00769-z","DOIUrl":"10.1007/s40291-024-00769-z","url":null,"abstract":"<p><strong>Background: </strong>In the diagnosis of sexually transmitted infections, there has been a demand for multiple molecular assays to rapidly and simultaneously detect not only pathogens but also drug resistance-associated mutations.</p><p><strong>Methods: </strong>In this study, we developed a new rapid simultaneous molecular assay for the detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium, and M. genitalium macrolide (23S rRNA gene, A2058/A2059) and fluoroquinolone (ParC gene, S83I) drug resistance-associated mutations in approximately 35 minutes. We evaluated the basic and prospective clinical performance of the newly developed assay.</p><p><strong>Results: </strong>The newly developed assay showed sufficient sensitivity to detect N. gonorrhoeae, C. trachomatis, T. vaginalis, and M. genitalium relative to the reference method. In a prospective study comparing the reference method across 178 urine samples from men and women, the total concordance rate, sensitivity, and specificity of the two assays for N. gonorrhoeae detection were 98.9% (176/178), 97.9% (46/47), and 99.2% (130/131), respectively; for C. trachomatis detection, they were 98.3% (175/178), 96.4% (81/84), and 100% (94/94); and for M. genitalium detection, they were 100% (178/178), 100% (20/20), and 100% (158/158). All samples were negative for T. vaginalis. Of the 16 M. genitalium-positive samples analyzed for the GENECUBE^TM assay, 81.3% (13/16) had A2058/A2059 mutations, 31.3% (5/16) had S83I mutations, and 25.0% (4/16) had simultaneous mutations, which was highly correlated with the sequence analysis.</p><p><strong>Conclusions: </strong>This study suggests that the recently developed assay performed similarly to existing nucleic acid amplification tests and enables rapid and simultaneous detection, including the detection of drug resistance-associated mutations.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"263-272"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014885","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":"Multicenter In-House Evaluation of an Amplicon-Based Next-Generation Sequencing Panel for Comprehensive Molecular Profiling.","authors":"Eloisa Jantus-Lewintre, Alessandra Rappa, Dina Ruano, Demi van Egmond, Sandra Gallach, Dilce Gozuyasli, Cecília Durães, José Luis Costa, Carlos Camps, Ludovic Lacroix, Karl Kashofer, Tom van Wezel, Massimo Barberis","doi":"10.1007/s40291-024-00766-2","DOIUrl":"10.1007/s40291-024-00766-2","url":null,"abstract":"<p><strong>Background: </strong>Predicting response to targeted cancer therapies increasingly relies on both simple and complex genetic biomarkers. Comprehensive genomic profiling using high-throughput assays must be evaluated for reproducibility and accuracy compared with existing methods.</p><p><strong>Methods: </strong>This study is a multicenter evaluation of the Oncomine™ Comprehensive Assay Plus (OCA Plus) Pan-Cancer Research Panel for comprehensive genomic profiling of solid tumors. A series of 193 research samples (125 DNA and 68 RNA samples) was analyzed to evaluate the correlation and concordance of the OCA Plus panel with orthogonal methods, as well as its reproducibility (n = 5 DNA samples) across laboratories.</p><p><strong>Results: </strong>The success rate for DNA and RNA sequencing was 96.6% and 89.7%, respectively. In a single workflow, the OCA Plus panel provided a detailed genomic profile with a high success rate for all biomarkers tested: single nucleotide variants/indels, copy number variants, and fusions, as well as complex biomarkers such as microsatellite instability, tumor mutational burden, and homologous recombination deficiency. The concordance for single nucleotide variants/indels was 94.8%, for copy number variants 96.5%, for fusions 94.2%, for microsatellite instability 80.8%, for tumor mutational burden 81.3%, and for homologous recombination deficiency 100%. The results showed high reproducibility across the five European research centers, each analyzing shared pre-characterized tissue biopsies (average of 1890 single nucleotide variants/indels per sample).</p><p><strong>Conclusions: </strong>This multicenter evaluation of the OCA Plus panel confirms the results of previous single-center studies and demonstrates the high reproducibility and accuracy of this assay.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"249-261"},"PeriodicalIF":4.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967330","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}