Pub Date : 2024-10-24DOI: 10.1016/j.jmoldx.2024.03.011
Yi-Wei Tang , Barbara A. Zehnbauer
{"title":"Navigating the Flood","authors":"Yi-Wei Tang , Barbara A. Zehnbauer","doi":"10.1016/j.jmoldx.2024.03.011","DOIUrl":"10.1016/j.jmoldx.2024.03.011","url":null,"abstract":"","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 11","pages":"Pages 950-951"},"PeriodicalIF":3.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512119","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}
Pub Date : 2024-10-24DOI: 10.1016/j.jmoldx.2024.08.003
Emily H. Essex
{"title":"25 Years of Publishing The Journal of Molecular Diagnostics","authors":"Emily H. Essex","doi":"10.1016/j.jmoldx.2024.08.003","DOIUrl":"10.1016/j.jmoldx.2024.08.003","url":null,"abstract":"","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 11","pages":"Pages 943-944"},"PeriodicalIF":3.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512118","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}
Pub Date : 2024-10-24DOI: 10.1016/j.jmoldx.2024.06.011
Pawel Mroz , Mark D. Ewalt , Susan E. Harley , Patricia C. Tsang , Rena R. Xian , Craig R. Soderquist
{"title":"The Era of Molecular Hematopathology","authors":"Pawel Mroz , Mark D. Ewalt , Susan E. Harley , Patricia C. Tsang , Rena R. Xian , Craig R. Soderquist","doi":"10.1016/j.jmoldx.2024.06.011","DOIUrl":"10.1016/j.jmoldx.2024.06.011","url":null,"abstract":"","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 11","pages":"Pages 945-949"},"PeriodicalIF":3.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512120","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}
Pub Date : 2024-10-21DOI: 10.1016/j.jmoldx.2024.09.005
Julie W Hirschhorn, N Esther Babady, Allen Bateman, Heather M Blankenship, Jennifer Dien Bard, Kelsey Florek, Paige M K Larkin, Marie-Claire Rowlinson, Kelly Wroblewski, Donna M Wolk
Next-generation sequencing (NGS) has applications in research, epidemiology, oncology, and infectious disease diagnostics. Wide variability exists in NGS wet laboratory techniques and dry laboratory analytical considerations. Thus, many questions remain unanswered when NGS methods are implemented in laboratories for infectious disease testing. Although this review is not intended to answer all questions, the most pressing questions from a public health and clinical hospital-based laboratory perspective will be addressed. The authors of this review are laboratory professionals who perform and interpret severe acute respiratory syndrome coronavirus 2 NGS results. Considerations for pre-analytical, analytical, and postanalytical NGS will be explored. This review highlights challenges for molecular laboratory professionals considering adopting or expanding NGS methods.
{"title":"Considerations for Severe Acute Respiratory Syndrome Coronavirus 2 Genomic Surveillance: A Joint Consensus Recommendation of the Association for Molecular Pathology and Association of Public Health Laboratories.","authors":"Julie W Hirschhorn, N Esther Babady, Allen Bateman, Heather M Blankenship, Jennifer Dien Bard, Kelsey Florek, Paige M K Larkin, Marie-Claire Rowlinson, Kelly Wroblewski, Donna M Wolk","doi":"10.1016/j.jmoldx.2024.09.005","DOIUrl":"10.1016/j.jmoldx.2024.09.005","url":null,"abstract":"<p><p>Next-generation sequencing (NGS) has applications in research, epidemiology, oncology, and infectious disease diagnostics. Wide variability exists in NGS wet laboratory techniques and dry laboratory analytical considerations. Thus, many questions remain unanswered when NGS methods are implemented in laboratories for infectious disease testing. Although this review is not intended to answer all questions, the most pressing questions from a public health and clinical hospital-based laboratory perspective will be addressed. The authors of this review are laboratory professionals who perform and interpret severe acute respiratory syndrome coronavirus 2 NGS results. Considerations for pre-analytical, analytical, and postanalytical NGS will be explored. This review highlights challenges for molecular laboratory professionals considering adopting or expanding NGS methods.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512117","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}
Pub Date : 2024-10-18DOI: 10.1016/j.jmoldx.2024.09.006
Kate Sears, Caylin Hickey, Ryan Vincent, Jennifer Stocks-Candelaria, Jason Tate, Cody Bumgardner, Shulin Zhang, Justin B Miller
Medical exome sequencing pipelines consist of various preprocessing steps to prioritize credible causal variants before a pathologist or variant curation scientist manually interprets potential findings that are then reported to patients. The variant allele frequency (VAF), reported as the fraction of sequencing reads supporting a variant call, can be used to screen for technical artifacts, yet a specific filtering threshold has yet to be established. A total of 13,122 manually curated variants, sequenced from 289 patients using the Agilent SureSelect Focused Exome enrichment kit at the University of Kentucky Clinical Genomics laboratory from October 2019 to May 2023, were evaluated. Totals of 278 single-nucleotide polymorphisms (SNPs) and 3340 SNPs as technical artifacts are clinically reported. All reported variants had a VAF between 0.33 and 0.63, and 82% (2725/3340) of sequencing artifacts had a VAF of <0.33. It is proposed that removing SNPs in which the VAF is less than approximately 0.30 reduces manual curation time by approximately 20% while capturing all medically relevant variants in medical exome sequencing data sets.
{"title":"Establishing a Variant Allele Frequency Cutoff for Manual Curation of Medical Exome Sequencing Data.","authors":"Kate Sears, Caylin Hickey, Ryan Vincent, Jennifer Stocks-Candelaria, Jason Tate, Cody Bumgardner, Shulin Zhang, Justin B Miller","doi":"10.1016/j.jmoldx.2024.09.006","DOIUrl":"10.1016/j.jmoldx.2024.09.006","url":null,"abstract":"<p><p>Medical exome sequencing pipelines consist of various preprocessing steps to prioritize credible causal variants before a pathologist or variant curation scientist manually interprets potential findings that are then reported to patients. The variant allele frequency (VAF), reported as the fraction of sequencing reads supporting a variant call, can be used to screen for technical artifacts, yet a specific filtering threshold has yet to be established. A total of 13,122 manually curated variants, sequenced from 289 patients using the Agilent SureSelect Focused Exome enrichment kit at the University of Kentucky Clinical Genomics laboratory from October 2019 to May 2023, were evaluated. Totals of 278 single-nucleotide polymorphisms (SNPs) and 3340 SNPs as technical artifacts are clinically reported. All reported variants had a VAF between 0.33 and 0.63, and 82% (2725/3340) of sequencing artifacts had a VAF of <0.33. It is proposed that removing SNPs in which the VAF is less than approximately 0.30 reduces manual curation time by approximately 20% while capturing all medically relevant variants in medical exome sequencing data sets.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479408","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}
Pub Date : 2024-10-02DOI: 10.1016/j.jmoldx.2024.09.004
Adil Menon, Madina Sukhanova, Kevin L. Nocito, Juehua Gao, Lawrence J. Jennings, Erica R. Vormittag-Nocito
Clonal hematopoiesis (CH) and clonal cytopenia of undetermined significance (CCUS) are recently recognized diagnostic entities that serve as independent risk factors for cardiovascular disease and myeloid malignancy. CH is an incidental finding, and evaluation of the incidence of CH/CCUS-associated mutations in solid tumor next-generation sequencing samples was undertaken to better understand the prevalence of mutations in this population. A retrospective review of clinical sequencing data for solid tumor malignancies diagnosed between February 2022 and April 2023 on next-generation sequencing data was performed. Cases were reviewed for variants in genes associated with CH/CCUS. Variant allele frequencies and other factors of the sequencing data were assessed for determining risk of CH/CCUS. A total of 2479 cases were evaluated during the study period. Of these, 29 cases demonstrated potential CH/CCUS-associated mutations, with a total of 33 variants identified. These were identified in a variety of tumor types, with gliomas being the most common. Significant cardiac histories were found in over half of cases identified, and few cases had abnormal blood counts. Detailed criteria for flagging variants as suspicious for CH and recommendations for these criteria as future guidelines for reporting are described. These variants are incidental findings that require more extensive follow-up or change in therapy management using a single institutional cohort.
{"title":"Detection and Interpretation of Clonal Hematopoiesis Variants during Routine Solid Tumor Next-Generation Sequencing","authors":"Adil Menon, Madina Sukhanova, Kevin L. Nocito, Juehua Gao, Lawrence J. Jennings, Erica R. Vormittag-Nocito","doi":"10.1016/j.jmoldx.2024.09.004","DOIUrl":"10.1016/j.jmoldx.2024.09.004","url":null,"abstract":"<div><div>Clonal hematopoiesis (CH) and clonal cytopenia of undetermined significance (CCUS) are recently recognized diagnostic entities that serve as independent risk factors for cardiovascular disease and myeloid malignancy. CH is an incidental finding, and evaluation of the incidence of CH/CCUS-associated mutations in solid tumor next-generation sequencing samples was undertaken to better understand the prevalence of mutations in this population. A retrospective review of clinical sequencing data for solid tumor malignancies diagnosed between February 2022 and April 2023 on next-generation sequencing data was performed. Cases were reviewed for variants in genes associated with CH/CCUS. Variant allele frequencies and other factors of the sequencing data were assessed for determining risk of CH/CCUS. A total of 2479 cases were evaluated during the study period. Of these, 29 cases demonstrated potential CH/CCUS-associated mutations, with a total of 33 variants identified. These were identified in a variety of tumor types, with gliomas being the most common. Significant cardiac histories were found in over half of cases identified, and few cases had abnormal blood counts. Detailed criteria for flagging variants as suspicious for CH and recommendations for these criteria as future guidelines for reporting are described. These variants are incidental findings that require more extensive follow-up or change in therapy management using a single institutional cohort.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 12","pages":"Pages 1149-1158"},"PeriodicalIF":3.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373414","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}
Pub Date : 2024-09-30DOI: 10.1016/j.jmoldx.2024.08.008
Mohamed A. Jama , N. Scott Reading , Eric Fredrickson , Sherin Shaaban , Yuan Ji
Mutation analysis provides confirmation of a clinical and radiological diagnosis of thanatophoric dysplasia types I and II (TD I and II). We developed a single multiplexed PCR and a single-nucleotide extension (SNE) assay to identify 14 common mutations causing 99% of TD I and TD II, including the challenging three adjacent mutations in the stop codon of exon 18 of the FGFR3 gene. The assay design also provides a solution for resolving SNE PCR product sizing using performance optimized polymer-7. The assay was validated using 37 previously characterized, de-identified patient samples representing the nine wild-types and 10 of 14 mutant genotypes. Four artificial templates were synthesized to mimic four TD I mutations not represented in the available patient samples. Fragment size and fluorophore channel for each SNE product from 10 samples and the four artificial templates were used to define bins and panels for analysis with GeneMarker version 3.0 and GeneMapper version 6.0 software. Allele calls (bin placement within the panels) were verified using the remaining 27 previously characterized samples. This TD I and II PCR and SNE assay is a robust multiplexed assay, streamlined, to identify 14 mutations in one single reaction. This assay has a shorter turnaround time in comparison to traditional Sanger or next-generation sequencing.
{"title":"A Single Multiplex PCR and Single-Nucleotide Extension Assay for the Detection of Common Thanatophoric Dysplasia I and II Mutations","authors":"Mohamed A. Jama , N. Scott Reading , Eric Fredrickson , Sherin Shaaban , Yuan Ji","doi":"10.1016/j.jmoldx.2024.08.008","DOIUrl":"10.1016/j.jmoldx.2024.08.008","url":null,"abstract":"<div><div>Mutation analysis provides confirmation of a clinical and radiological diagnosis of thanatophoric dysplasia types I and II (TD I and II). We developed a single multiplexed PCR and a single-nucleotide extension (SNE) assay to identify 14 common mutations causing 99% of TD I and TD II, including the challenging three adjacent mutations in the stop codon of exon 18 of the <em>FGFR3</em> gene. The assay design also provides a solution for resolving SNE PCR product sizing using performance optimized polymer-7. The assay was validated using 37 previously characterized, de-identified patient samples representing the nine wild-types and 10 of 14 mutant genotypes. Four artificial templates were synthesized to mimic four TD I mutations not represented in the available patient samples. Fragment size and fluorophore channel for each SNE product from 10 samples and the four artificial templates were used to define bins and panels for analysis with GeneMarker version 3.0 and GeneMapper version 6.0 software. Allele calls (bin placement within the panels) were verified using the remaining 27 previously characterized samples. This TD I and II PCR and SNE assay is a robust multiplexed assay, streamlined, to identify 14 mutations in one single reaction. This assay has a shorter turnaround time in comparison to traditional Sanger or next-generation sequencing.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 12","pages":"Pages 1102-1108"},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367258","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}
Pub Date : 2024-09-30DOI: 10.1016/j.jmoldx.2024.08.007
Silvia A. Longhi , Lady J. García-Casares , Arturo Muñoz-Calderón , Lucía Irazu , Marcelo A. Rodríguez , Gustavo Landfried , Julio Alonso-Padilla , Alejandro G. Schijman , Chagas-Group
Timely diagnosis of vertical Trypanosoma cruzi infections involves microscopy-based detection of circulating parasites from peripheral blood, which lacks sensitivity and is operator dependent. Consequently, most children born to T. cruzi–infected mothers are required to undergo serological testing after 9 months, which risks loss to follow-up. Alternatively, the loop-mediated isothermal amplification (LAMP) test for T. cruzi DNA offers high analytical and clinical performance and is easy to use in low-complexity laboratories. Recently, we optimized this technique using an ultrarapid DNA extraction method combined with the LAMP in dried blood spots (DBSs) on Flinders Technology Associates cards. The procedure has been implemented in 10 public maternities across Paraguay, Bolivia, and Argentina, involving the training of 14 technicians. Operators' performance was evaluated using a standardized DBS testing panel for harmonization, including negative controls and DBS samples artificially contaminated with T. cruzi at 50 and 20 cells/mL. There was strong agreement (ĸ = 0.924) for controls and 50 cells/mL samples, and good agreement (ĸ = 0.718) across all testing panels, even at the detection limit of the test. A prospective study collected 306 DBSs from 222 newborns at birth and/or 2 months, detecting T. cruzi microscopically in four cases. LAMP identified eight positive cases and perfectly aligned with real-time PCR (ĸ = 1), demonstrating higher sensitivity than microscopic observation for early detection of infection in infants.
{"title":"Interlaboratory Harmonization Study and Prospective Evaluation of the PURE–Trypanosoma cruzi–Loop-Mediated Isothermal Amplification Assay for Detecting Parasite DNA in Newborn's Dried Blood Spots","authors":"Silvia A. Longhi , Lady J. García-Casares , Arturo Muñoz-Calderón , Lucía Irazu , Marcelo A. Rodríguez , Gustavo Landfried , Julio Alonso-Padilla , Alejandro G. Schijman , Chagas-Group","doi":"10.1016/j.jmoldx.2024.08.007","DOIUrl":"10.1016/j.jmoldx.2024.08.007","url":null,"abstract":"<div><div>Timely diagnosis of vertical <em>Trypanosoma cruzi</em> infections involves microscopy-based detection of circulating parasites from peripheral blood, which lacks sensitivity and is operator dependent. Consequently, most children born to <em>T. cruzi</em>–infected mothers are required to undergo serological testing after 9 months, which risks loss to follow-up. Alternatively, the loop-mediated isothermal amplification (LAMP) test for <em>T. cruzi</em> DNA offers high analytical and clinical performance and is easy to use in low-complexity laboratories. Recently, we optimized this technique using an ultrarapid DNA extraction method combined with the LAMP in dried blood spots (DBSs) on Flinders Technology Associates cards. The procedure has been implemented in 10 public maternities across Paraguay, Bolivia, and Argentina, involving the training of 14 technicians. Operators' performance was evaluated using a standardized DBS testing panel for harmonization, including negative controls and DBS samples artificially contaminated with <em>T. cruzi</em> at 50 and 20 cells/mL. There was strong agreement (ĸ = 0.924) for controls and 50 cells/mL samples, and good agreement (ĸ = 0.718) across all testing panels, even at the detection limit of the test. A prospective study collected 306 DBSs from 222 newborns at birth and/or 2 months, detecting <em>T. cruzi</em> microscopically in four cases. LAMP identified eight positive cases and perfectly aligned with real-time PCR (ĸ = 1), demonstrating higher sensitivity than microscopic observation for early detection of infection in infants.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 12","pages":"Pages 1055-1064"},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367259","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}
Pub Date : 2024-09-26DOI: 10.1016/j.jmoldx.2024.08.004
Carmen Rubio-Alarcón , Ellen Stelloo , Daan C.L. Vessies , Iris van 't Erve , Nienke J. Mekkes , Joost Swennenhuis , Soufyan Lakbir , Elisabeth J. van Bree , Marianne Tijssen , Pien Delis-van Diemen , Mirthe Lanfermeijer , Theodora Linders , Daan van den Broek , Cornelis J.A. Punt , Jaap Heringa , Gerrit A. Meijer , Sanne Abeln , Harma Feitsma , Remond J.A. Fijneman
Structural variants (SVs) caused by chromosomal rearrangements in common fragile sites or long interspersed nuclear element (LINE) retrotranspositions are highly prevalent in colorectal cancer. However, methodology for the targeted detection of these SVs is lacking. This article reports the use of formalin-fixed, paraffin-embedded targeted-locus capture (FFPE-TLC) sequencing as a novel technology for the targeted detection of tumor-specific SVs. Analysis of 29 FFPE colorectal tumor samples and 8 matched normal samples revealed tumor-specific SVs in 24 patients (83%), with a median of 2 SVs per patient (range, 1 to 21). A total of 104 SVs were found in the common fragile site–associated genes MACROD2, PRKN, FHIT, and WWOX in 18 patients (62%), and 39 SVs caused by three LINE transposable elements were found in 15 patients (52%). Tumor specificity of SVs was independently verified by droplet digital PCR of tumor tissue DNA, and their applicability as plasma circulating tumor DNA biomarkers was demonstrated. FFPE-TLC sequencing enabled the detection of tumor-specific SVs caused by chromosomal rearrangements and LINE retrotranspositions in FFPE tissue. Therefore, FFPE-TLC sequencing facilitates the investigation of the biological and clinical effects of SVs using FFPE material from (retrospective) cohorts of cancer patients and has potential clinical applicability in the detection of SV biomarkers in the routine molecular diagnostics setting.
{"title":"High Prevalence of Chromosomal Rearrangements and LINE Retrotranspositions Detected in Formalin-Fixed, Paraffin-Embedded Colorectal Cancer Tissue","authors":"Carmen Rubio-Alarcón , Ellen Stelloo , Daan C.L. Vessies , Iris van 't Erve , Nienke J. Mekkes , Joost Swennenhuis , Soufyan Lakbir , Elisabeth J. van Bree , Marianne Tijssen , Pien Delis-van Diemen , Mirthe Lanfermeijer , Theodora Linders , Daan van den Broek , Cornelis J.A. Punt , Jaap Heringa , Gerrit A. Meijer , Sanne Abeln , Harma Feitsma , Remond J.A. Fijneman","doi":"10.1016/j.jmoldx.2024.08.004","DOIUrl":"10.1016/j.jmoldx.2024.08.004","url":null,"abstract":"<div><div>Structural variants (SVs) caused by chromosomal rearrangements in common fragile sites or long interspersed nuclear element (LINE) retrotranspositions are highly prevalent in colorectal cancer. However, methodology for the targeted detection of these SVs is lacking. This article reports the use of formalin-fixed, paraffin-embedded targeted-locus capture (FFPE-TLC) sequencing as a novel technology for the targeted detection of tumor-specific SVs. Analysis of 29 FFPE colorectal tumor samples and 8 matched normal samples revealed tumor-specific SVs in 24 patients (83%), with a median of 2 SVs per patient (range, 1 to 21). A total of 104 SVs were found in the common fragile site–associated genes <em>MACROD2</em>, <em>PRKN</em>, <em>FHIT</em>, and <em>WWOX</em> in 18 patients (62%), and 39 SVs caused by three LINE transposable elements were found in 15 patients (52%). Tumor specificity of SVs was independently verified by droplet digital PCR of tumor tissue DNA, and their applicability as plasma circulating tumor DNA biomarkers was demonstrated. FFPE-TLC sequencing enabled the detection of tumor-specific SVs caused by chromosomal rearrangements and LINE retrotranspositions in FFPE tissue. Therefore, FFPE-TLC sequencing facilitates the investigation of the biological and clinical effects of SVs using FFPE material from (retrospective) cohorts of cancer patients and has potential clinical applicability in the detection of SV biomarkers in the routine molecular diagnostics setting.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 12","pages":"Pages 1065-1080"},"PeriodicalIF":3.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331459","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}
Pub Date : 2024-09-26DOI: 10.1016/j.jmoldx.2024.09.002
Alba Abras
{"title":"Isothermal Nucleic Acid Amplification as a Promising and Versatile Diagnostic Approach for Point-of-Care Testing of Congenital Chagas Disease","authors":"Alba Abras","doi":"10.1016/j.jmoldx.2024.09.002","DOIUrl":"10.1016/j.jmoldx.2024.09.002","url":null,"abstract":"","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 12","pages":"Pages 1042-1044"},"PeriodicalIF":3.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331461","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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