Molecular Diagnosis & Therapy最新文献

{"title":"Fluorescence Imaging-Assessed Surgical Margin Detection in Head and Neck Oncology by Passive and Active Targeting.","authors":"L Dirheimer, S Cortese, G Dolivet, J L Merlin, F Marchal, R Mastronicola, L Bezdetnaya","doi":"10.1007/s40291-025-00781-x","DOIUrl":"10.1007/s40291-025-00781-x","url":null,"abstract":"<p><p>Surgery remains the gold standard in the management of head and neck squamous cell carcinoma (HNSCC). However, the anatomical complexity of these cancers, combined with the difficulty in discriminating between healthy and cancerous tissue and the detection of microlesions, complicates tumor resection, resulting in positive surgical margins, which are associated with a poor patient prognosis. Fluorescence-guided surgery (FGS) has emerged as a promising technique in the management of HNSCC, improving tumor resection and margin assessment. FGS strategies can be roughly divided into three approaches; namely, natural tissue autofluorescence, passive delivery of fluorescent contrast agents, and active targeting. This review provides a comprehensive overview of the advances made in FGS of head and neck cancers, particularly aiming to improve surgical margin assessment. Recently, the field has shown promising results by addressing contrast agents targeted to the overexpressed epidermal growth factor receptor (EGFR), both in preclinical and clinical settings. The identification of new targets such as αVβ6 integrin, uPAR, PARP1, and so on, as well as the development of contrast agents, are key steps in the further development of FGS of head and neck cancers, making it an essential tool in precision oncology. Among these, as was demonstrated in preclinical studies, the αVβ6 integrin is emerging as a promising target due to its high and specific expression in tumor and tumor margins.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"465-481"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041776","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":"Evaluation of Minimal Residual Disease in Patients with Neuroblastoma.","authors":"Nobuyuki Yamamoto, Kikyo Ishizawa, Mayuno Umemoto, Akihiro Nishimura, Tomoko Fujikawa, Shotaro Inoue, Naoko Nakatani, Akihiro Tamura, Nanako Nino, Suguru Uemura, Daiichiro Hasegawa, Yoshiyuki Kosaka, Noriyuki Nishimura","doi":"10.1007/s40291-025-00788-4","DOIUrl":"10.1007/s40291-025-00788-4","url":null,"abstract":"<p><p>Neuroblastoma (NB) is a pediatric extracranial solid tumor that accounts for approximately 15% of all pediatric cancer deaths. More than 50% of patients with newly diagnosed NB are classified into a high-risk group with an approximately 50% long-term survival rate. Although most high-risk patients with NB achieve remission, more than half may have minimal residual disease (MRD) that eventually causes relapse. Looking towards an optimal outcome, the accurate evaluation of MRD in patients with NB (NB-MRD) is essential to monitor the treatment response and disease burden. Over the past decades, the quantification of NB-associated messenger RNA (NB-mRNA) by reverse transcriptase-polymerase chain reaction has become widely used to detect NB-MRD, owing to the lack of recurrent genomic aberrations in NB cells. To achieve a more accurate and sensitive detection, the current NB-MRD assays quantify a set of NB-mRNAs to detect NB cells in bone marrow, peripheral blood, and peripheral blood stem cell samples. Among a growing number of NB-MRD assays, several assays quantitating different but overlapping sets of NB-mRNAs are reported to have a significant prognostic value. However, the clinical significance of NB-MRD remains to be established. In this review, we summarize the recent progress in NB-MRD and evaluate its clinical value.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"443-452"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192436","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":"Fatty Acid Desaturase: The Yin or Yang of Disease Pathology.","authors":"Veeksha V Shetty, Shilpa S Shetty","doi":"10.1007/s40291-025-00796-4","DOIUrl":"https://doi.org/10.1007/s40291-025-00796-4","url":null,"abstract":"<p><p>Fatty acid desaturases are key enzymes in lipid metabolism, crucial for converting saturated fatty acids into monounsaturated fatty acids. This review examines the roles of stearoyl-CoA desaturase, fatty acid desaturase 1, fatty acid desaturase 2 and fatty acid desaturase 3 in health and disease, highlighting their impact on cellular functions such as membrane fluidity, signalling and energy homeostasis. Dysregulation of desaturase activity can have significant implications for human health, contributing to the development of various pathological conditions, including cardiovascular disease, metabolic disorders and cancer. Fatty acid desaturase 1 and fatty acid desaturase 2 overexpression in cancer correlates with tumour growth and chemoresistance, marking them as potential therapeutic targets. The development of inhibitors targeting stearoyl-CoA desaturase and fatty acid desaturase 1 offers promising therapeutic avenues for metabolic diseases and cancer. This review underscores the critical roles of desaturases in various diseases. It emphasises the need for ongoing research to develop effective diagnostic, prognostic and therapeutic strategies, ultimately improving patient outcomes in altered fatty acid metabolism conditions.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530736","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 and Genetic Profile of 35 Patients with Glycogen Storage Disease Type 1b: A Comparative Analysis Before and During SGLT2 Inhibitor Therapy.","authors":"Maja Djordjevic Milosevic, Anita Skakic, Bozica Kecman, Sara Stankovic, Ivona Kovacevic, Sonja Pavlovic, Maja Stojiljkovic","doi":"10.1007/s40291-025-00795-5","DOIUrl":"https://doi.org/10.1007/s40291-025-00795-5","url":null,"abstract":"<p><strong>Background: </strong>Glycogen storage disease type 1b (GSD 1b) is an ultra-rare disease worldwide, whereas in Serbia it has an unexpectedly high prevalence. GSD 1b is the result of variants in the SLC37A4 gene and reduced function of the enzyme glucose 6 phosphate translocase (G6PT). In addition to the classic symptoms of GSD 1a, patients with GSD 1b have neutropenia and impaired neutrophil function.</p><p><strong>Methods: </strong>The genotype and clinical profile were analyzed in 35 patients, 26 of whom were children. In all patients, pathogenic variants in the SLC37A4 gene were confirmed using Sanger or next-generation sequencing (NGS). Eight different variants were found. The following clinical data were analyzed: age at diagnosis, first symptoms of GSD 1b, severity of intestinal symptoms, lowest neutrophil count, mean hemoglobin value, height, body mass index (BMI), and quality of life. Patients were classified into four groups based on the severity of their intestinal symptoms.</p><p><strong>Results: </strong>In our study 30 patients received empagliflozin therapy. Our data are comprised of information from a total of 62 treatment years and include self-reported quality-of-life surveys before and during empagliflozin therapy. The average age at which empagliflozin was introduced in pediatric patients was 8.5 years, with the youngest two patients, both female, starting SGLT2 inhibitor therapy at the age of two.</p><p><strong>Conclusions: </strong>Our findings suggest that empagliflozin therapy significantly improves neutropenia recovery by reducing the frequency of recurrent infections and inflammatory bowel disease (IBD)-like symptoms. This improvement was demonstrated by a marked reduction in skin and mucosal infections, particularly oral ulcers, as well as an increase in hemoglobin levels and overall stature.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327537","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":"Advances in Understanding Long COVID: Pathophysiological Mechanisms and the Role of Omics Technologies in Biomarker Identification.","authors":"Mônica Duarte da Silva, Thamires Santos da Silva, Claudemir Gregório Mendes, Maria Carolina Miglino Valbão, Abraham Kwame Badu-Tawiah, Lucas Fornari Laurindo, Sandra Maria Barbalho, Rosa Direito, Maria Angélica Miglino","doi":"10.1007/s40291-025-00792-8","DOIUrl":"https://doi.org/10.1007/s40291-025-00792-8","url":null,"abstract":"<p><p>Long coronavirus disease (COVID) is a multisystem condition that affects a significant proportion of individuals following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with persistent symptoms ranging from fatigue and cognitive dysfunction to cardiovascular disorders. It is estimated that 30-60% of infected individuals experience symptoms lasting more than 12 weeks. Despite advances in understanding acute infection, the pathophysiological mechanisms underlying long COVID remain unclear. Current hypotheses suggest that viral persistence, immune dysfunction, and metabolic alterations play central roles. Omics approaches, including metabolomics, proteomics, and lipidomics, have played a crucial role in investigating molecular changes, identifying biomarkers, and refining therapeutic strategies. This review discusses recent advances in understanding long COVID, addressing its mechanisms, risk factors, the impact of viral variants, and the role of vaccination, with an emphasis on the importance of omics technologies in elucidating this condition.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327536","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":"The Role of MicroRNAs in the Pathogenesis and as Biomarkers for Pediatric Epilepsy: A Systematic Review.","authors":"Fady Zakaria, Steven Amged Yousef, Janna AbdelDayem, Rawan ElGamal, Omar Y Issa, Mohamed Mansour, Harvey Bastorous, Eslam Emad, Rudayna Mahgoub","doi":"10.1007/s40291-025-00791-9","DOIUrl":"https://doi.org/10.1007/s40291-025-00791-9","url":null,"abstract":"<p><strong>Purpose: </strong>Epilepsy is highly prevalent among children, making it one of the most common neurological diseases in the pediatric population. Its diagnosis is problematic, largely depending on clinical judgment and inaccurate investigative studies. Thus, a more objective investigation is warranted. MicroRNAs (miRNAs) are small molecules found in various body fluids and tissues that prove to have potential, as they play an important role in the pathogenesis of epilepsy. This review evaluates the use of miRNAs in the diagnosis, prediction, and prognosis of pediatric epilepsy. Furthermore, it discusses the use of miRNAs as therapeutic agents and the relationship between miRNAs and antiepileptic drugs (AEDs).</p><p><strong>Methods: </strong>From inception until 7 July 2024, a thorough search of PubMed, Europe PMC, PubMed Central, and Google Scholar was conducted.</p><p><strong>Results: </strong>Our review is based on 18 studies on pediatric patients with epilepsy according to the selection criteria. A total of 33 different miRNAs for diagnosis, 13 for prediction, and 2 for prognosis of pediatric epilepsy in a total sample size of 663, 111, and 163 pediatric patients, respectively, in addition to 20 miRNAs for the diagnosis of focal epilepsy, and a further 4 for generalized epilepsy in the same population were interpreted in our systematic review.</p><p><strong>Conclusions: </strong>These studies suggest that miRNA usage as a diagnostic, predictive, and prognostic biomarker for pediatric patients with epilepsy is promising. However, further research on that population is needed, as the number of studies is limited, with several bias concerns and heterogeneity, with the need for clinical trials to assess the use of miRNAs as drug agents. PROSPERO registration no. ID: PROSPERO 2024 CRD42024578258.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250563","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":"Current Methods in Clinical Alzheimer's Disease Research and Diagnosis.","authors":"Eleftheria Kodosaki, Henrik Zetterberg, Amanda Heslegrave","doi":"10.1007/s40291-025-00789-3","DOIUrl":"https://doi.org/10.1007/s40291-025-00789-3","url":null,"abstract":"<p><p>Early and accurate diagnosis of Alzheimer's disease is crucial for enabling timely intervention and improving patient outcomes. Recent advancements in molecular and imaging methodologies have significantly enhanced the detection of Alzheimer's disease at its early stages and have improved the quality of research in the field. Key molecular approaches include the identification of biomarkers such as amyloid-beta plaques and tau protein tangles, which are central to Alzheimer's disease pathology. These biomarkers can be detected through biofluid analysis or imaging methods, offering high sensitivity, however with disadvantages, which are discussed here. Despite the transition of some of these methods from research settings to clinical practice, several challenges persist, including the need for standardisation across diagnostic platforms and ensuring the accessibility of these advanced technologies within diverse healthcare systems. Additionally, the high cost and requirement for specialised expertise remain significant barriers. Here, we discuss the need to improve the effectiveness of early AD diagnosis, the ongoing research that is being conducted to refine biomarker detection, enhance imaging techniques and develop more cost-effective non-invasive diagnostic approaches. These advancements are essential to overcoming current limitations and ensuring a broader application in clinical settings.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250562","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":"Utilization of a Multi-modal Comprehensive Genomic and Immune Profiling Testing Strategy Results in a High Rate of Test Success and Detection of Clinically Relevant Biomarkers While Optimizing Tissue Usage.","authors":"Michelle F Green, Zachary D Wallen, Heidi C Ko, Kyle C Strickland, Alicia Dillard, Jeffrey M Conroy, Durga P Dash, Mary K Nesline, Paul DePietro, Shengle Zhang, Kamal S Saini, Pratheesh Sathyan, Marcia Eisenberg, Brian Caveney, Shakti Ramkissoon, Eric A Severson, Rebecca A Previs","doi":"10.1007/s40291-025-00793-7","DOIUrl":"https://doi.org/10.1007/s40291-025-00793-7","url":null,"abstract":"<p><strong>Background: </strong>Molecular profiling is quickly becoming standard for patients with advanced cancer, with an increasing number of biomarker-directed therapies and innovative precision diagnostics available. However, with the expansion of relevant biomarkers, clinicians often face challenges obtaining optimal detection from limited tumor tissue. Here, we present biomarker detection rates from comprehensive genomic and immune profiling (CGIP) performed as a component of routine clinical care using a multi-modal testing strategy.</p><p><strong>Methods: </strong>CGIP was performed on 20,645 solid tumor specimens in a CAP/CLIA and NYS CLEP-certified reference laboratory, including DNA- and RNA-based next-generation sequencing (NGS), RNA gene expression profiling, and PD-L1 immunohistochemistry (IHC). RNA and DNA were co-extracted to optimize tissue usage. Clinical significance of detected biomarkers was classified in accordance with the joint consensus recommendations of the Association for Molecular Pathology (AMP), American Society of Clinical Oncology (ASCO), and the College of American Pathologists (CAP).</p><p><strong>Results: </strong>Adequacy of specimens for analysis with each test component varied from 99.8% (20,612) for PD-L1 IHC to 87.7% (18,113) for RNA-based NGS. DNA-based NGS had a > 96.0% success rate across all result components (short variants, copy number alterations, and genomic signatures), while RNA-based NGS and gene expression profiling were successful for 92.1% (16,689) and 90.2% (17,275) of cases, respectively. Median turnaround time from specimen receipt in the testing laboratory to report delivery was 8 days (range 1-35). Within our cohort of 15,815 cases with complete results available, 61.0% (9650) had at least one tier 1 biomarker with known clinical significance, 88.8% (14,039) had at least one tier 2 biomarker with potential clinical significance, 57.5% (9,090) had both tier 1 and 2 biomarkers, and 7.7% (1216) had no clinically significant biomarkers detected. Biomarker detection rates varied across tumor types, increasing with the addition of testing modalities.</p><p><strong>Conclusions: </strong>Utilization of a multi-modal CGIP testing strategy resulted in a high rate of test success and detection of clinically relevant biomarkers while optimizing tissue usage.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250564","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 Actionability of Molecular Targets in Multi-Ethnic Breast Cancer Patients: A Retrospective Single-Institutional Study.","authors":"Irene Kang, Leah Naghi, Susan E Yost, Joanne Mortimer","doi":"10.1007/s40291-025-00777-7","DOIUrl":"10.1007/s40291-025-00777-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Precision oncology is making remarkable advancements in optimizing patient care by personalizing treatments. To date, the US Food and Drug Administration (FDA) has approved poly(ADP-ribose) polymerase inhibitors (PARPi) olaparib (Lynparza, AstraZeneca and Merck) and talazoparib (Talzenna, Pfizer Oncology Together™) for germline or somatic BRCA1/2-mutated metastatic breast cancer (BC) patients, and PI3K inhibitor alpelisib (Piqray, Novartis) plus fulvestrant for patients with hormone receptor-positive human epidermal growth factor receptor 2-negative (HR+HER2-) PIK3CA-mutated advanced BC. In addition, the FDA approved capivasertib (Trucap, AstraZeneca) for HR+HER2- locally advanced or metastatic BC patients with one or more AKT1, PIK3CA, or PTEN alterations. Finally, the FDA recently approved elacestrant (Orserdu, Stemline Therapeutics, Inc.) for postmenopausal patients with ER+ HER2- ESR1-mutated advanced or metastatic BC with disease progression following at least one line of endocrine therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study presents a single institutional retrospective review of genomic reports of patients with BC. Analysis of genomic reports of 1361 BC sequencing reports was performed for 1010 patients with BC from 2013 to 2023 (23% of patients had multiple reports). Eligible patients had at least one primary or metastatic tumor. Multiple sequencing platforms were used for FFPE specimens including Tempus xT targeted next-generation sequencing (NGS), Foundation One Medicine, HopeSeq, Ashion Analytics GEM ExTra, and Exact Sciences Oncomap. Liquid biopsies were performed by Guardant, Tempus, and Foundation One Medicine. Chart reviews were performed to collect patient characteristics. BRCA1/2-mutated, metastatic BC patients who initiated treatment with olaparib or talazoparib, and PIK3CA-mutated, HR+ metastatic BC patients who initiated treatment with alpelisib were reported. In addition, patients with ESR1 or AKT1/PIK3CA/PTEN mutations were identified. Clinical outcomes, including progression-free survival (PFS) and overall survival (OS) were analyzed for BRCA1/2 and PIK3CA-mutated patients who received PARPi or alpelisib. Survival curves were generated using the Kaplan Meier method.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A cohort of 1010 BC patients with 1361 genomic reports was identified. A total of 935/1361 (69%) specimens were formalin-fixed paraffin-embedded (FFPE) tumor biopsies and 426/1361 (31%) were liquid biopsies. Receptor status included 65% HR+HER2-, 8% HR+HER2+, 4% HR-HER2+, and 23% TNBC. Racial and ethnic distribution of these patients included 50% non-Hispanic White, 26% Hispanic, 17% Asian, 6% African American, 1% other (Native Hawaiian or Other Pacific Islander, American Indian or Alaska Native, or unknown). Sequencing platforms included 30% Tempus xT, 31% Foundation One, 10% HopeSeq, 20% GEM ExTra, and 9% Exact Sciences. Liquid biopsies included 79% Guardant, 20% Tempus, and 1% Foundation O","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"393-405"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796840","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":"Identification of Somatic Genetic Variants in Superficial Vascular Malformations by Liquid Biopsy in a Cohort of 88 Patients from a French Hospital.","authors":"Franck Neil El Sissy, Annouk Bisdorff, Alexandre Perrier, Erell Guillerm, Jérôme Denis, Löetitia Favre, Mathilde Aubertin, Mélanie Eyries, Florence Coulet","doi":"10.1007/s40291-025-00770-0","DOIUrl":"10.1007/s40291-025-00770-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Superficial vascular anomalies are complex disorders characterized by abnormal vascular growth. Next-generation sequencing has recently identified somatic genetic alterations associated with these malformations, offering new insights for targeted treatments. However, tissue biopsies for genetic testing can be invasive and difficult to obtain, especially in arteriovenous malformations (AVM) with hemorrhagic risks. A liquid biopsy, a non-invasive approach, offers a promising solution by detecting genetic mutations in cell-free DNA. This pilot study aimed to evaluate the feasibility of using a liquid biopsy for the genetic analysis of patients with superficial vascular anomalies through cell-free DNA sampling. Additionally, it explored whether specific sampling sites, such as the afferent artery, nidus, and efferent vein, could enhance the sensitivity of detecting pathogenic variants in patients with AVM.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 88 patients were enrolled, including 55 with AVM and 33 with lymphatic malformations. For patients with AVM, cell-free DNA samples were collected from peripheral blood, efferent veins, afferent arteries, and the AVM nidus. In patients with lymphatic malformations, cystic lymphatic fluid was collected by a direct puncture during diagnostic procedures. A molecular analysis was performed using a targeted gene panel relevant to somatic alterations in solid tumors. Pathogenic variants were validated by digital polymerase chain reaction for patients with lymphatic malformations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Pathogenic variants were identified in 23.6% of patients with AVM, predominantly in MAP2K1 and KRAS genes, with higher sensitivity near the AVM nidus. In addition, pathogenic variants were identified in 27.3% of patients with lymphatic malformations, all involving the PIK3CA gene. Despite the lower sensitivity of a cell-free DNA analysis compared with a tissue biopsy, especially in patients with AVM, the detection rate suggests the utility for a cell-free DNA analysis, particularly when a tissue biopsy is not feasible.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study confirms the feasibility of using a cell-free DNA liquid biopsy for genotyping patients with superficial vascular anomalies, although a tissue biopsy remains the gold standard for comprehensive genetic profiling because of its higher sensitivity. A liquid biopsy offers a non-invasive option for molecular analysis that is useful as a preliminary or alternative approach when direct tissue sampling is not possible. Importantly, the sensitivity of cell-free DNA sampling in AVM appeared highest when obtained close to the nidus, indicating an optimal sampling location for future studies. Further research is needed to improve detection sensitivity, especially for samples taken near the nidus, to validate and strengthen these findings. Although our study focused on superficial/extra-cranial AVM, further rese","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"367-380"},"PeriodicalIF":4.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081451","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}