Journal of Molecular Diagnostics最新文献

Diagnosis of Australasian Patients with Neuromuscular Disease 澳大利亚神经肌肉疾病患者的诊断

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-06-24 DOI: 10.1016/j.jmoldx.2025.03.011

Carolin K. Scriba , Fathimath Faiz , Michael Black , Rebecca Gooding , Padma Sivadorai , Daniel Trajanoski , Adriana Botero , Cheryl Wise , Gianina Ravenscroft , Mark R. Davis , Nigel G. Laing

{"title":"Diagnosis of Australasian Patients with Neuromuscular Disease","authors":"Carolin K. Scriba , Fathimath Faiz , Michael Black , Rebecca Gooding , Padma Sivadorai , Daniel Trajanoski , Adriana Botero , Cheryl Wise , Gianina Ravenscroft , Mark R. Davis , Nigel G. Laing","doi":"10.1016/j.jmoldx.2025.03.011","DOIUrl":"10.1016/j.jmoldx.2025.03.011","url":null,"abstract":"<div><div>Neurogenetic disorders are a large group of genetic and phenotypically heterogeneous diseases, making diagnosis challenging. Sequencing hundreds of disease genes concurrently using massively parallel sequencing is, therefore, invaluable for diagnosis of these disorders. The PathWest neuromuscular disease gene panels include all known genes associated with neurologic and muscle disorders. Initially implemented in 2013, covering 336 genes, the gene panel has undergone various updates in chemistries and seen the addition of many newly described neurogenic disease genes. The results from versions 3 and 5 of the panel are reported, which included 644 and 830 genes, respectively. In total, 3961 patients were tested across 20 phenotypic subpanels: 2740 on version 3 and 1221 on version 5. Overall diagnostic success was 23.0%, with 8.4% of diagnoses attributed to newly added genes. Diagnostic success varied greatly between phenotypic subpanels, from 63.4% for the congenital muscular dystrophy subpanel to 2.6% for the Alzheimer disease/frontotemporal dementia subpanel. The five most frequently reported genes, DMD, RYR1, SPG7, PMP22, and NOTCH3, accounted for 22% of all diagnoses. Changing chemistries improved coverage of regions that were previously not well resolved. This enabled improved copy number variant calling, with 10.5% of diagnoses from version 5 attributed to copy number variants. The data generated have enabled identification of factors broadly affecting diagnosis of neuromuscular disorders and potential limitations hampering diagnostic success.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"27 7","pages":"Pages 630-644"},"PeriodicalIF":3.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366246","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 performance evaluation of a tiling amplicon panel for whole genome sequencing of respiratory syncytial virus. 呼吸道合胞病毒全基因组测序切片扩增子面板的临床性能评价。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-06-19 DOI: 10.1016/j.jmoldx.2025.05.005

B Ethan Nunley, Amelia Weixler, Hyeong Geon Kim, Hong Xie, Jaydee Sereewit, Pooneh Hajian, Sean Ellis, Margaret G Mills, Ailyn C Pérez-Osorio, Stephanie Goya, Jolene Gov, Rebecca Dewar, Goncalo Fernandes, Kate E Templeton, Daniel M Maloney, Alexander L Greninger, Pavitra Roychoudhury

{"title":"Clinical performance evaluation of a tiling amplicon panel for whole genome sequencing of respiratory syncytial virus.","authors":"B Ethan Nunley, Amelia Weixler, Hyeong Geon Kim, Hong Xie, Jaydee Sereewit, Pooneh Hajian, Sean Ellis, Margaret G Mills, Ailyn C Pérez-Osorio, Stephanie Goya, Jolene Gov, Rebecca Dewar, Goncalo Fernandes, Kate E Templeton, Daniel M Maloney, Alexander L Greninger, Pavitra Roychoudhury","doi":"10.1016/j.jmoldx.2025.05.005","DOIUrl":"10.1016/j.jmoldx.2025.05.005","url":null,"abstract":"Accurate genomic characterization of respiratory syncytial virus (RSV) is crucial for studies of epidemiology and viral evolution, including monitoring potential escape from newly authorized vaccines and prophylactic monoclonal antibodies. We adapted a viral genome tiling amplicon panel (UW-ARTIC) and developed a custom bioinformatic pipeline for high-throughput, cost-effective sequencing of both RSV-A and RSV-B subgroups. We established genome acceptability criteria and determined the performance characteristics of the panel including assay sensitivity, specificity, breadth of genome recovery, accuracy, and precision using contrived and remnant clinical specimens. High-quality genomes (>95% genome completeness; >500X and >1000X average depth for whole genome and fusion gene respectively) were recovered from samples with Ct ≤ 30 (∼594 and 2,004 copies per reaction for RSV-A and RSV-B respectively). Minor variants were accurately identified at >5% allele frequency. The assay showed high accuracy when compared to Sanger, shotgun metagenomic, and hybridization capture-based sequencing, as well as high repeatability and reproducibility. The UW-ARTIC RSV panel has utility for cost-effective RSV genome recovery in public health, clinical, and research applications. It has been used to generate FDA-reportable data for clinical trials of RSV antiviral products, with robust performance in global samples from as recently as the 2023/24 season. Continued genomic surveillance and future updates to primers will be essential for continued recovery of genomes as RSV continues to evolve.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340561","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

Screening G6PD mutation in blood donors by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry with high-throughput and multiple targets. 基质辅助激光解吸/电离飞行时间质谱高通量多靶点筛查献血者G6PD突变

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-06-19 DOI: 10.1016/j.jmoldx.2025.05.004

Ziyan Li, Zhenyi Huang, Mengxi Li, Yunshan Cao, Yating Li, Jinlv Liu, Suping Zhong, Lijuan Lin, Yanping Fang, Zhaoying Su, Yongxin Huang, Wanjun Zhou, Lingxiao Jiang

{"title":"Screening G6PD mutation in blood donors by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry with high-throughput and multiple targets.","authors":"Ziyan Li, Zhenyi Huang, Mengxi Li, Yunshan Cao, Yating Li, Jinlv Liu, Suping Zhong, Lijuan Lin, Yanping Fang, Zhaoying Su, Yongxin Huang, Wanjun Zhou, Lingxiao Jiang","doi":"10.1016/j.jmoldx.2025.05.004","DOIUrl":"10.1016/j.jmoldx.2025.05.004","url":null,"abstract":"Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited disorder worldwide and is particularly prevalent in historically malaria-endemic countries. In this study, we established a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) assay for G6PD mutation detection. This MALDI-TOF-MS assay with single base extension (SBE) was developed to efficiently and accurately test 19 common G6PD variants in the Chinese population. The MALDI-TOF-MS assay was used to analyze a total of 2,205 peripheral blood samples, including 1,111 normal individuals and 1,094 G6PD gene mutation carriers. All 2,205 sample results were validated by Sanger sequencing in a blinded study. The MALDI-TOF-MS assay developed in this study was applied to detect G6PD mutations in 300 uncharacterized blood donor samples, of which 17 (5.56%) were found to carry G6PD gene mutations. Basic characteristics of regarding the 17 blood donors were summarized and followed up. In this study, a MALDI-TOF-MS assay was applied to blood donors to detect common G6PD mutations in Guangdong, China, which provided a new concept for establishing the information regarding the blood bank database of G6PD deficiency donors.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340562","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

Value of molecular autopsy in suspected sudden cardiac death in the young. 分子解剖在疑似青年心源性猝死中的价值。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-06-19 DOI: 10.1016/j.jmoldx.2025.05.006

Mònica Coll, Mireia Alcalde, Anna Fernández-Falgueras, Anna Iglesias, Laia Nogué-Navarro, Coloma Tiron, Oscar Campuzano, Marisa Ortega, Santiago Crespo, Eneko Barberia, Ramon Brugada

{"title":"Value of molecular autopsy in suspected sudden cardiac death in the young.","authors":"Mònica Coll, Mireia Alcalde, Anna Fernández-Falgueras, Anna Iglesias, Laia Nogué-Navarro, Coloma Tiron, Oscar Campuzano, Marisa Ortega, Santiago Crespo, Eneko Barberia, Ramon Brugada","doi":"10.1016/j.jmoldx.2025.05.006","DOIUrl":"10.1016/j.jmoldx.2025.05.006","url":null,"abstract":"Genetic testing, as part of the medico-legal autopsy in cases of suspected sudden cardiac death, has been recommended for several years, however, are rarely performed. The aim was to assess the value of postmortem genetic testing in unexplained sudden death in the young. This is a prospective study including all cases with unexplained natural sudden death cases in individuals ≤50 years old undergoing a legal autopsy. Postmortem genetic testing was routinely performed in cases under 35 and after 35 only when no cause of death was identified or there was suspicion of a possible inherited cardiac phenotype after a complete autopsy. In cases under 35 years of age, genetic testing showed a positivity rate of 7.6%. The most striking finding has been the positivity rate of thoracic aorta aneurysms and myocarditis cases at 33% respectively. In cases between 36 and 50 years of age, the positivity rate was 4.9%. If we were to approach this group with direct genetic analysis, as we did with the younger cohort, the yield of positive genetic testing would drop to 2.5%. This is the largest study of postmortem genetic testing in the young to date, and the first to address its value in consecutive cases, free of selection bias.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340563","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 Clinical Molecular Laboratories for Detection of Homologous Recombination Deficiency in Cancer: A Joint Consensus Recommendation of the Association of Molecular Pathology, Association of Cancer Care Centers, and College of American Pathologists. 对检测癌症同源重组缺陷的临床分子实验室的建议：分子病理学协会、癌症护理中心协会和美国病理学家学院的联合共识建议。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-06-13 DOI: 10.1016/j.jmoldx.2025.05.003

Susan J Hsiao, Destin Black, Kelly A Devereaux, Ian S Hagemann, Lawrence J Jennings, Diana Mandelker, Vera A Paulson, Michelle Shiller, Tracy L Stockley, Eric Vail, Praveen Vikas, Anna Yemelyanova

{"title":"Recommendations for Clinical Molecular Laboratories for Detection of Homologous Recombination Deficiency in Cancer: A Joint Consensus Recommendation of the Association of Molecular Pathology, Association of Cancer Care Centers, and College of American Pathologists.","authors":"Susan J Hsiao, Destin Black, Kelly A Devereaux, Ian S Hagemann, Lawrence J Jennings, Diana Mandelker, Vera A Paulson, Michelle Shiller, Tracy L Stockley, Eric Vail, Praveen Vikas, Anna Yemelyanova","doi":"10.1016/j.jmoldx.2025.05.003","DOIUrl":"10.1016/j.jmoldx.2025.05.003","url":null,"abstract":"Homologous recombination deficiency (HRD) is a genomic feature present in some malignant neoplasms and is attributed to the failure of the homologous recombination repair pathway. Tumors with an HRD-positive status may have a distinct prognosis and/or response to therapies, including poly (ADP-ribose) polymerase inhibitors. The Association for Molecular Pathology assembled an expert panel to examine current practice and perform a scoping review of the medical literature pertaining to the molecular detection of HRD in the clinical setting. The expert panel examined the following topics: components of existing and proposed HRD and genomic instability biomarkers (including mutational signatures, loss of heterozygosity, mutations in homologous recombination repair-associated genes, and epigenetic silencing of RAD51C, BRCA1, or BRCA2); technical considerations for identifying genomic scars from tumor and germline next-generation sequencing results; guidelines on interpretation and caveats when reporting assessments of genomic instability and HRD scores; and the clinical significance of HRD. The panel formulated a set of expert consensus opinion recommendations regarding HRD assay design and validation to guide laboratories in developing HRD tests to ensure high-quality and reproducible results.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303456","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

Evaluating Discordant Somatic Calls Across Mutation Discovery Approaches to Minimize False-Negative Drug-Resistant Findings. 评估突变发现方法中不一致的体细胞呼叫，以尽量减少假阴性耐药结果。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-06-13 DOI: 10.1016/j.jmoldx.2025.04.012

Hsin-Fu Lin, Pei-Miao Chien, Chinyi Cheng, Tzu-Hang Yuan, Yu-Bin Wang, Pei-Lung Chen, Chien-Yu Chen, Jia-Hsin Huang, Jacob Shujui Hsu

{"title":"Evaluating Discordant Somatic Calls Across Mutation Discovery Approaches to Minimize False-Negative Drug-Resistant Findings.","authors":"Hsin-Fu Lin, Pei-Miao Chien, Chinyi Cheng, Tzu-Hang Yuan, Yu-Bin Wang, Pei-Lung Chen, Chien-Yu Chen, Jia-Hsin Huang, Jacob Shujui Hsu","doi":"10.1016/j.jmoldx.2025.04.012","DOIUrl":"10.1016/j.jmoldx.2025.04.012","url":null,"abstract":"Evaluating robustness of somatic mutation detections is essential when using whole-exome sequencing (WES) for treatment decision-making. A comprehensive evaluation was conducted using tumor WES from the US Food and Drug Administration-led Sequencing Quality Control Phase 2 project, in which multiple library kits sequenced identical DNA materials across three laboratories to benchmark analytical validity. These workflows included various read aligner (BWA, Bowtie2, DRAGEN-Aligner, DRAGMAP, and HISAT2) and mutation caller (Mutect2, TNscope, DRAGEN-Caller, and DeepVariant) combinations. The results revealed that DRAGEN exhibited superior performance, achieving mean F1 scores of 0.966 and 0.791 for single-nucleotide variant and insertion/deletion detection, respectively. Among open-source software, BWA Mutect2 and HISAT2 Mutect2 combinations showed the highest mean F1 scores for single-nucleotide variant (0.949) and insertion/deletion (0.722), respectively. The analyses indicated that high-quality data can be analyzed as having worse results, and vice versa. Evaluations of Catalog of Somatic Mutations in Cancer reported mutations unveiled discrepancies across enrichment kits. IDT enrichment kits showed a higher false-negative rate, whereas Agilent WES kits tended to miss mutations in CBL and IDH1, and Roche library kits tended to miss the mutations in PIK3CB. For drug-related biomarkers, Sentieon TNscope tended to underestimate tumor mutation burden and overlook crucial drug-resistance mutations, such as FLT3 (c.G1879A: p.A627T) for cytarabine resistance in leukemia and MAP2K1 (c.G199A:p.D67N) for BRAF inhibitors in melanoma. The findings highlight the importance of robust bioinformatic analysis in identifying tumor mutations and guiding clinical decision-making.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303454","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

Morphological Bone Score as a Predictive Tool for Molecular Profiling Success. 形态学骨评分作为分子谱分析成功的预测工具。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-06-13 DOI: 10.1016/j.jmoldx.2025.04.013

Kirill Kriukov, Dmitry Ivchenkov, Anna Bejanyan, Aleksandr Sarachakov, Aleksandra Kviatkovskaia, Gleb Khegai, Dominique Knipper-Davis, Amber Berlinski, Tayla Soares, Jochen Lennerz, Vladimir Kushnarev

{"title":"Morphological Bone Score as a Predictive Tool for Molecular Profiling Success.","authors":"Kirill Kriukov, Dmitry Ivchenkov, Anna Bejanyan, Aleksandr Sarachakov, Aleksandra Kviatkovskaia, Gleb Khegai, Dominique Knipper-Davis, Amber Berlinski, Tayla Soares, Jochen Lennerz, Vladimir Kushnarev","doi":"10.1016/j.jmoldx.2025.04.013","DOIUrl":"10.1016/j.jmoldx.2025.04.013","url":null,"abstract":"Decalcification of bone-containing tumor samples serves to soften tissues before histologic processing. However, it can lead to nucleic acid degradation, resulting in next-generation sequencing failures that impede diagnostic solutions for patients. The Morphological Bone Score (MBS) described herein optimizes the assessment of decalcified tissue samples, consequently improving both diagnostic accuracy and cost efficiency in molecular genetic laboratories. The MBS, constructed using five key morphologic features, assigns scores from 0 to 11, reflecting low to high tissue damage and direct proportionality with nucleic acid yields per cell. The MBS threshold can be adjusted, depending on the aims of a specific analysis while balancing between sensitivity and accuracy. In our next-generation sequencing workflow, the exclusion of poor-quality samples from downstream processing using MBS led to a savings of $1500 per sample. The MBS provides a cost-effective approach for maximizing tissue utilization and optimizing downstream profiling in precision oncology because its objectivity and consistency in evaluating pathologic samples ensure reliable and reproducible outcomes. With additional verification, this tool could be implemented in computational models for converting morphologic features into measurable units.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Comparative Study of Medium-Coverage Genome Sequencing and SNP Array Technology in Identifying Chromosomal Abnormalities to Advance Prenatal and Postnatal Diagnosis. 中覆盖基因组测序和SNP阵列技术在染色体异常识别中的比较研究，以促进产前和产后诊断。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-06-06 DOI: 10.1016/j.jmoldx.2025.04.009

Jialun Pang, Lin Zhou, Jiancheng Hu, Hanzhe Kuang, Hui Xi, Na Ma, Shuting Yang, Wenxian Yu, Yanan Zhang, Qian Zhang, Victor Wei Zhang, Jing Chen, Ying Peng

{"title":"A Comparative Study of Medium-Coverage Genome Sequencing and SNP Array Technology in Identifying Chromosomal Abnormalities to Advance Prenatal and Postnatal Diagnosis.","authors":"Jialun Pang, Lin Zhou, Jiancheng Hu, Hanzhe Kuang, Hui Xi, Na Ma, Shuting Yang, Wenxian Yu, Yanan Zhang, Qian Zhang, Victor Wei Zhang, Jing Chen, Ying Peng","doi":"10.1016/j.jmoldx.2025.04.009","DOIUrl":"10.1016/j.jmoldx.2025.04.009","url":null,"abstract":"This study aimed to compare the performance of 5-fold genome sequencing (GS) with single nucleotide polymorphism (SNP) array technology in detecting chromosomal abnormalities, particularly in the context of prenatal and postnatal diagnostics. A total of 42 samples, previously analyzed by SNP array, were re-examined using 5-fold GS to evaluate the detection of clinically significant copy number variations (CNVs), mosaicism, and absence of heterozygosity (AOH). The results revealed a 100% concordance between the two methods for the identification of clinically relevant CNVs, with both technologies detecting similar CNV size ranges. However, 5-fold GS demonstrated better precision in defining CNV breakpoints and exhibited a lower false-positive rate, as confirmed by quantitative PCR validation. Additionally, 5-fold GS detected mosaicism with comparable sensitivity to SNP array, capturing mosaic levels as low as 17%, whereas SNP array identified levels between 15% and 84%. For AOH detection, 5-fold GS identified all candidate AOH regions with a slightly better sensitivity, achieving a detection size limit of 4.8 Mb compared with SNP array's 5.08 Mb. Overall, 5-fold GS shows potential as a reliable method for chromosomal abnormality detection, offering high accuracy and clinical utility in both prenatal and postnatal genetic testing.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250605","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 of Human Papillomavirus Genotyping by Oxford Nanopore Sequencing in Formalin-Fixed, Paraffin-Embedded Tissues and ThinPrep Anal and Gynecologic Samples. 牛津纳米孔测序在FFPE组织和ThinPrep肛门和妇科样本中的HPV基因分型验证。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-06-05 DOI: 10.1016/j.jmoldx.2025.04.010

Carolina Hernandez, Luz H Patiño, Milena Camargo, Ching Yi Wang, Feng Chen, Bernadette Liggayu, Liyong Cao, Carlos Cordon-Cardo, Emilia M Sordillo, Alberto Paniz-Mondolfi, Juan D Ramírez

{"title":"Validation of Human Papillomavirus Genotyping by Oxford Nanopore Sequencing in Formalin-Fixed, Paraffin-Embedded Tissues and ThinPrep Anal and Gynecologic Samples.","authors":"Carolina Hernandez, Luz H Patiño, Milena Camargo, Ching Yi Wang, Feng Chen, Bernadette Liggayu, Liyong Cao, Carlos Cordon-Cardo, Emilia M Sordillo, Alberto Paniz-Mondolfi, Juan D Ramírez","doi":"10.1016/j.jmoldx.2025.04.010","DOIUrl":"10.1016/j.jmoldx.2025.04.010","url":null,"abstract":"Human papillomavirus (HPV) is linked to various cancers, including cervical, anal, and head and neck cancers. Conventional methods for HPV genotyping and commercial platforms are limited to detecting high-risk HPV genotypes primarily in gynecologic samples. Because of changing trends in the epidemiology and pathogenesis, there is a growing need for HPV genotyping techniques applicable to emerging clinical contexts involving diverse sample types, such as head and neck or anal samples, particularly for formalin-fixed, paraffin-embedded (FFPE) tissues. This study aimed to validate amplicon-based sequencing with Oxford Nanopore Technologies (ONT) for the detection and genotyping of HPV in 181 samples, including FFPE head and neck samples, and ThinPrep liquid-based cytology samples from anal and gynecologic tissues. Sanger sequencing was used as a reference for genotyping accuracy. The ONT sequencing method demonstrated a limit of detection of 1 copy/μL for HPV16 and HPV18. Perfect agreement (κ coefficient = 1.0) was observed for HPV detection across all sample types. Genotyping accuracy exceeded 95%, and ONT identified additional genotypes in certain anal and gynecologic samples that were undetected by Sanger sequencing. The assay showed high reproducibility, with consistent results across intrarun and interrun analyses. This study is the first to validate ONT sequencing for HPV genotyping in FFPE head and neck samples. ONT provides a rapid, cost-effective method for comprehensive HPV genotyping in diverse sample types.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250607","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

Comparison of the Mutational Profile between BCL2- and BCL6-Rearrangement Positive Follicular Lymphoma. BCL2-和bcl6重排阳性滤泡性淋巴瘤突变谱的比较。

IF 3.4 3区医学

Journal of Molecular Diagnostics Pub Date : 2025-06-05 DOI: 10.1016/j.jmoldx.2025.05.002

Haruka Ikoma, Joaquim Carreras, Yara Yukie Kikuti, Masashi Miyaoka, Shunsuke Nagase, Yusuke Kondo, Atsushi Ito, Makoto Orita, Sakura Tomita, Shinichiro Hiraiwa, Hiroshi Kawada, Juan F Garcia, Giovanna Roncador, Elias Campo, Naoya Nakamura

{"title":"Comparison of the Mutational Profile between BCL2- and BCL6-Rearrangement Positive Follicular Lymphoma.","authors":"Haruka Ikoma, Joaquim Carreras, Yara Yukie Kikuti, Masashi Miyaoka, Shunsuke Nagase, Yusuke Kondo, Atsushi Ito, Makoto Orita, Sakura Tomita, Shinichiro Hiraiwa, Hiroshi Kawada, Juan F Garcia, Giovanna Roncador, Elias Campo, Naoya Nakamura","doi":"10.1016/j.jmoldx.2025.05.002","DOIUrl":"10.1016/j.jmoldx.2025.05.002","url":null,"abstract":"It was recently reported that follicular lymphoma (FL) with BCL6 rearrangement (R) is associated with favorable progression-free survival, whereas BCL2-R and BCL2-6-R cases are associated with disease progression. However, the pathologic mechanism remained unexplored. This study analyzed the mutational landscape and immune microenvironment of 31 FL cases, including 16 BCL2-R, 11 BCL6-R, and 4 BCL2-6-R FL cases. The method included an in-house next-generation targeted sequencing panel of 168 genes associated with aggressive B-cell lymphoma and FL, whole genome copy number change microarray (OncoScan), and immunohistochemistry for the immune microenvironment focused on M2-like tumor-associated macrophages, regulatory T lymphocytes, and programmed cell death protein 1 (PDCD1; alias PD-1)-positive follicular T helper cells. The resulting mutational profile was compatible with a previously reported conventional FL series featuring frequent mutations in CREBBP, KMT2D, TNFRSF14, STAT6, and CD36. Moreover, BCL6-R cases had mutations in ARID1B, ARID5B, and RHOA; low frequency of mutations in other genes, such as OSBPL10, PTPRD, ATM, and HLA-B; 6q loss; and absence of disease progression. In comparison with BCL6-R cases, BCL2-R and BCL2-6-R cases had mutations in EZH2, chromosome 18 copy number gain, and disease progression in some cases. The immune microenvironment profile was heterogeneous; however, BCL6-R cases demonstrated higher infiltration of colony-stimulating factor 1 receptor- and leukocyte immunoglobulin like receptor B3 (LILRB3; alias CD85a)-positive cells. In conclusion, compared with BCL2-R, FL with BCL6-R exhibited some differences in mutational profiles and immune microenvironment.","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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