Molecular Diagnosis & Therapy最新文献

{"title":"Multi-Institutional Evaluation of Interrater Agreement of Biomarker-Drug Pair Rankings Based on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) and Sources of Discordance.","authors":"Alexandra Lebedeva, Ekaterina Belova, Alexandra Kavun, Anastasiia Taraskina, Michele Bartoletti, Ivan Bièche, Giuseppe Curigliano, Célia Dupain, Alejandro Rios-Hoyo, Maud Kamal, Claudio Luchini, Stanislav Poyarkov, Christophe Le Tourneau, Egor Veselovsky, Vladislav Mileyko, Maxim Ivanov","doi":"10.1007/s40291-024-00748-4","DOIUrl":"10.1007/s40291-024-00748-4","url":null,"abstract":"<p><strong>Background: </strong>The widespread use of next-generation sequencing in clinical practice has contributed to the accumulation of a large number of genomic findings associated with targeted therapy; therefore, the problem of ranking the detected findings has become acute. The European Society for Medical Oncology Scale of Clinical Actionability of molecular Targets (ESCAT) system was designed by the European Society for Medical Oncology to rank biomarkers into levels of evidence that reflect their potency and clinical significance based on published clinical data. However, the ESCAT system remains imperfect, as it is based on a subjective assessment of the levels of evidence.</p><p><strong>Objective: </strong>The objective of this study was to determine whether the ranking of LOE for biomarker-drug pairs based on the ESCAT system is dependent on the human factor, and to uncover potential issues associated with the use of the framework.</p><p><strong>Methods: </strong>To evaluate the inter-rater agreement, we created a dataset of a total of 154 biomarker-drug pairs for 18 unique tumor types. We aimed to include biomarker-drug pairs that could be considered standard of care as well as less common and under investigated pairs. Fourteen precision oncology experts were invited to assign an ESCAT level of evidence for biomarker-drug pairs. Statistical analysis was carried out using Cohen's kappa and the Kolmogorov-Smirnov test.</p><p><strong>Results: </strong>The inter-rater agreement was low with some exceptions, and significant deviations from the consensus level of evidence were observed. For biomarker-drug associations, the deviations from the consensus were observed for more than 50% of the contributors' rankings. The most agreement between the contributors was observed for lung adenocarcinoma (p < 0.005), while the most disagreement was observed for esophageal cancer (p < 0.01) biomarker-drug pairs in our dataset.</p><p><strong>Conclusions: </strong>This study demonstrates noteworthy discordances between the precision oncology experts and may provide the directions for future developments in modifying the ESCAT framework and the overall applicability of the results of genomic profiling into clinical practice.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"91-101"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378504","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":"Diagnostic Utility of a 90-Gene Expression Assay (Canhelp-Origin) for Patients with Metastatic Cancer with an Unclear or Unknown Diagnosis.","authors":"Peng Qi, Yifeng Sun, Yue Pang, Jing Liu, Xu Cai, Shenglin Huang, Qinghua Xu, Qifeng Wang, Xiaoyan Zhou","doi":"10.1007/s40291-024-00746-6","DOIUrl":"10.1007/s40291-024-00746-6","url":null,"abstract":"<p><strong>Background: </strong>Metastatic cancers with unclear or unknown origins pose significant challenges in diagnosis and management, frequently leading to suboptimal outcomes. Studies have demonstrated that a 90-gene expression assay is effective in predicting the primary origin and guiding the site-specific therapy to improve prognosis. This study aimed to evaluate the clinical effectiveness of a 90-gene expression assay in patients with unclear or unknown diagnoses.</p><p><strong>Methods: </strong>The study encompassed patients for whom a 90-gene expression assay was requested as part of standard care. Data on patient demographics, tumor characteristics, and clinical history were collected. The assay's performance was evaluated by comparing its predicted tumor type with the final histopathological diagnosis.</p><p><strong>Results: </strong>Among 303 cases analyzed, a 90-gene expression assay successfully identified a molecular-based tumor type for 295 (97.4%) patients. Comparison with histopathological diagnosis revealed an overall agreement of 88.5% (170/192). In patients with a single suspected primary site (n = 140), the assay confirmed the suspected diagnosis in 90.7% of cases. For those with a differential diagnosis (n = 52), the assay narrowed down the possibilities in 82.7% of cases. Moreover, in cases where the histopathology report indicated cancer of unknown primary (n = 103), the assay offered a molecular tumor type prediction with potential clinical significance.</p><p><strong>Conclusions: </strong>This study demonstrates the significant impact of a 90-gene expression assay on diagnosis and potential treatment selection for difficult-to-diagnose patients, highlighting its clinical value as a standardized molecular approach to streamline further diagnostic testing for patients with metastatic cancer of unclear or unknown origin. Further prospective study is required to assess whether employing molecular diagnostic classifiers enhances clinical outcomes in these patients.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"81-89"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331120","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":"Correction to: Molecular Therapeutics in Development to Treat Alzheimer's Disease.","authors":"Maria Carmela Tartaglia, Martin Ingelsson","doi":"10.1007/s40291-024-00752-8","DOIUrl":"10.1007/s40291-024-00752-8","url":null,"abstract":"","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"143"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548602","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":"Triple Tracer PET in Advanced Prostate Cancer: Chasing Phenotypic Plasticity.","authors":"Luca Urso, Matteo Brunelli, Luca Filippi","doi":"10.1007/s40291-024-00760-8","DOIUrl":"10.1007/s40291-024-00760-8","url":null,"abstract":"","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"5-8"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774117","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":"Emerging RNAi Therapies to Treat Hypertension.","authors":"Pawan Daga, Gurnoor Singh, Tushar Menon, Maryta Sztukowska, Dinesh K Kalra","doi":"10.1007/s40291-024-00747-5","DOIUrl":"10.1007/s40291-024-00747-5","url":null,"abstract":"<p><p>Hypertension (HTN), often dubbed the \"silent killer,\" poses a significant global health challenge, affecting over 1.3 billion individuals. Despite advances in treatment, effective long-term blood pressure (BP) control remains elusive, necessitating novel therapeutic approaches. Poor control of BP remains a leading cause of cardiovascular morbidity and mortality worldwide and is becoming an even larger global health problem due to the aging population, rising rates of obesity, poorer dietary patterns and overall cardiometabolic health, and suboptimal rates of patient adherence and optimal BP control. Ribonucleic acid interference (RNAi) technology, which leverages the body's natural gene-silencing mechanism, has emerged as a promising strategy for several diseases and has recently been tested for its antihypertensive effects. We systematically reviewed peer-reviewed articles from databases including PubMed, EMBASE, and Scopus for studies examining RNAi's role in managing HTN, focusing on mechanisms, clinical utility, and safety profile. Key early-phase trials of some RNAi-leading candidate drugs are detailed. Also highlighted are challenges such as target specificity, delivery mechanisms, durability of effect, and immunogenicity. We conclude by summarizing how RNAi has a significant potential role in HTN therapy due to their unique benefits, such as long-term duration of action, infrequent dosing, and lack of major side effects.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"25-41"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479162","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":"Extracellular Histones Profiles of Pediatric H3K27-Altered Diffuse Midline Glioma.","authors":"Diana Buzova, Lucia Lisa Petrilli, Jan Frohlich, Desislava K Tsoneva, Salvatore Daniele Bianco, Maria Rita Braghini, Anna Alisi, Angela Mastronuzzi, Jan Cerveny, Tommaso Mazza, Maria Vinci, Manlio Vinciguerra","doi":"10.1007/s40291-024-00754-6","DOIUrl":"10.1007/s40291-024-00754-6","url":null,"abstract":"<p><strong>Background: </strong>Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in the midline structures of the brain. When located in the pons, it is more commonly referred to as diffuse intrinsic pontine glioma (DIPG). DMG/DIPG is usually diagnosed when children are < 10 years, and it has a median overall survival of < 12 months after diagnosis. Radiological imaging is still the gold standard for DIPG diagnosis while the use of biopsy procedures led to our knowledge on its biology, such as with the identification of the canonical histone H3K27M mutation. However, the need to improve survival encourages the development of non-invasive, fast and inexpensive assays on biofluids for optimizing molecular diagnoses in DMG/DIPG. Here, we propose a rapid, new, imaging and epigenetics-based approach to diagnose DMG/DIPG in the plasma of paediatric patients.</p><p><strong>Methods: </strong>A total of 20 healthy children (mean age: 10.5 years) and 24 children diagnosed with DMG/DIPG (mean age: 8.5 years) were recruited. Individual histones (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2), histone dimers and nucleosomes were assayed in biofluids by means of a new advanced flow cytometry ImageStream(X)-adapted method.</p><p><strong>Results: </strong>We report a significant increase in circulating histone dimers and tetramers (macroH2A1.1/H2B versus control: p value < 0.0001; macroH2A1.2/H2B versus control: p value < 0.0001; H2A/H2B versus control: p value < 0.0001; H3/H4 versus control: p value = 0.008; H2A/H2B/H3/H4 versus control: p value < 0.0001) and a significant downregulation of individual histones (H2B versus control: p value < 0.0001; H3 versus control: p value < 0.0001; H4 versus control: p value < 0.0001). Moreover, histones were also detectable in the cerebrospinal fluid (CSF) of patients with DMG/DIPG and in the supernatant of SF8628, OPBG-DIPG002 and OPBG-DIPG004 DMG/DIPG cell lines, with patterns mostly similar to each other, but distinct compared to blood plasma.</p><p><strong>Conclusions: </strong>In summary, we identified circulating histone signatures able to detect the presence of DMG/DIPG in biofluids of children, using a rapid and non-invasive ImageStream(X)-based imaging technology, which may improve diagnosis and benefit the patients.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"129-141"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607256","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":"Molecular Therapeutics in Development to Treat Alzheimer's Disease.","authors":"Maria Carmela Tartaglia, Martin Ingelsson","doi":"10.1007/s40291-024-00738-6","DOIUrl":"10.1007/s40291-024-00738-6","url":null,"abstract":"<p><p>Until recently, only symptomatic therapies, in the form of acetylcholine esterase inhibitors and NMDA-receptor antagonists, have been available for the treatment of Alzheimer's disease. However, advancements in our understanding of the amyloid cascade hypothesis have led to a development of disease-modifying therapeutic strategies. These include immunotherapies based on an infusion of monoclonal antibodies against amyloid-β, three of which have been approved for the treatment of Alzheimer's disease in the USA (one of them, lecanemab, has also been approved in several other countries). They all lead to a dramatic reduction of amyloid plaques in the brain, whereas their clinical effects have been more limited. Moreover, they can all lead to side effects in the form of amyloid-related imaging abnormalities. Ongoing developments aim at facilitating their administration, further improving their effects and reducing the risk for amyloid-related imaging abnormalities. Moreover, a number of anti-tau immunotherapies are in clinical trials, but none has so far shown any robust effects on symptoms or pathology. Another line of development is represented by gene therapy. To date, only antisense oligonucleotides against amyloid precursor protein/amyloid-β and tau have reached the clinical trial stage but a variety of gene editing strategies, such as clustered regularly interspaced short palindromic repeats/Cas9-mediated non-homologous end joining, base editing, and prime editing, have all shown promise on preclinical disease models. In addition, a number of other pharmacological compounds targeting a multitude of biochemical processes, believed to be centrally involved in Alzheimer's disease, are currently being evaluated in clinical trials. This article delves into current and future perspectives on the treatment of Alzheimer's disease, with an emphasis on immunotherapeutic and gene therapeutic strategies.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"9-24"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308929","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":"Targeted Therapy in Salivary Gland Cancer: Prevalence of a Selected Panel of Actionable Molecular Alterations in a German Tertiary Referral Center Patient Cohort.","authors":"Maximilian Linxweiler, Silke Wemmert, Felix Leon Braun, Sandrina Körner, Lukas Alexander Brust, Moritz Knebel, Gilbert Georg Klamminger, Mathias Wagner, Luc G T Morris, Jan Philipp Kühn","doi":"10.1007/s40291-024-00750-w","DOIUrl":"10.1007/s40291-024-00750-w","url":null,"abstract":"<p><strong>Objective: </strong>Salivary gland carcinomas (SGC) are a heterogeneous group of malignancies, with 24 subtypes defined by the World Health Organization (WHO). The standard of therapy is surgical resection, with adjuvant radiotherapy in most cases. However, disease recurrence (R) or metastasis (M) is common and no active systemic therapies are currently available for RM-SGC resulting in a 5-year survival rate of only 20%.</p><p><strong>Patients and methods: </strong>Overall, 55 SGC patients with seven different histological tumor subtypes were included in this study. formalin-fixed paraffin-embedded (FFPE) tissue samples were used for immunohistochemical (IHC) staining targeting HER2/neu, androgen receptor (AR), PD-L1, EGFR, panTRK, and TROP2. Fluorescence in situ hybridization (FISH) was performed for detecting HER2/neu amplifications and NTRK1/2/3 translocations in selected cases with relevant HER2/neu and panTRK protein expression, respectively. IHC and FISH results were correlated with patients' clinical and histopathological data.</p><p><strong>Results: </strong>The overall prevalence of druggable molecular alterations, defined as an immunoreactive score ≥ 9 in at least one of the analyzed targets, was 54.4% with the highest percentage in oncocytic carcinomas (100%) and lowest percentage in acinic cell carcinomas (10%). EGFR overexpression proved to be the most common alteration (32.7% of cases) followed by overexpression of TROP2 (27.3%), AR (10.9%), HER2/neu (7.3%), PD-L1 (1.8%), and panTRK (1.8%). HER2/neu amplifications were found in 50% and NTRK translocations were found in 100% of all cases with elevated Her2/neu and panTRK protein expression, respectively.</p><p><strong>Conclusions: </strong>Our data indicate that targeted therapy using e.g., trastuzumab deruxtecan, bicalutamide, pembrolizumab, cetuximab, entrectinib or sacituzumab govitecan might be a promising option especially for a relevant subset of patients with RM-SGC not suitable for salvage surgery. However, evidence from clinical studies regarding response rates to these therapies remains sparse, which underlines the need of multicenter clinical trials.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"103-115"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562958","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":"Emerging Radiopharmaceuticals in Pet Imaging for Mesothelioma: A Review of [¹⁸F]FDG Alternatives.","authors":"Priscilla Guglielmo, Cinzia Crivellaro, Angelo Castello, Carminia Maria Della Corte, Maria Pagano, Silvia Marchesi, Mario Occhipinti, Paolo Andrea Zucali, Laura Evangelista","doi":"10.1007/s40291-024-00756-4","DOIUrl":"10.1007/s40291-024-00756-4","url":null,"abstract":"<p><p>Mesothelioma is a malignant tumor associated primarily with asbestos exposure, characterized by an aggressive nature and poor prognosis. Accurate diagnosis, staging, and monitoring of therapeutic response are crucial for effective patient management. Along with a computed tomography (CT) scan, fluorodeoxyglucose labeled with fluorine-18 ([¹⁸F]FDG) positron emission tomography (PET) is commonly used in mesothelioma evaluation. However, it has some limitations, including lower sensitivity after pleurodesis and poor accuracy for involved lymph node evaluation. Thus, there is the need to explore other agents. The aim of the present review is to analyze the current literature on the use of alternative radiopharmaceuticals for PET imaging in patients with mesothelioma. A comprehensive search of scientific databases (PubMed, Scopus, and Web of Science) for studies published in the last decade was performed by using the following keywords: \"mesothelioma\" AND \"PET\" AND \"PET/CT\" \"radiopharmaceuticals\", \"[¹⁸F]FDG alternatives\". Articles focused solely on [¹⁸F]FDG, non-English publications or preclinical studies, reviews, meeting abstracts, letters to the editors, and editorials were excluded. A qualitative assessment was made by using the Critical Appraisal Skills Programme (CASP) checklist for diagnostic test studies, when applicable. In total, 14 papers were selected; in seven articles more than five patients were enrolled, while the other seven were only clinical cases (enrolling up to two subjects). [¹⁸F]/gallium-68 ([⁶⁸Ga])-labeled fibroblast activation protein inhibitor (FAPI) compounds, [¹⁸F]Fluorothymidine ([¹⁸F]FLT), methionine labeled with carbon-11 ([¹¹C]MET), and fluoromisonidazole labeled with fluorine-18 ([¹⁸F]FMISO) PET/CT were the alternative agents used most often. In 12 articles, [¹⁸F]FDG PET/CT was used as a comparator imaging modality. Detection rate of [¹⁸F]FDG was similar to the other radiopharmaceuticals ([⁶⁸Ga]/[18F]-labeled FAPI compounds, [¹⁸F]FLT, [¹⁸F]FMISO, [¹¹C]MET, and [⁶⁸Ga]-Pentaxifor), although radiolabeled FAPI seems to exhibit a higher diagnostic performance. [¹⁸F]FDG is still a valuable agent in patients with mesothelioma. However, radiolabeled FAPI appears to be promising and its theranostic properties should therefore be further assessed.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"55-66"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607252","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":"Real-World Evidence of the Prevalence of Driver Mutations in Anorectal Melanoma.","authors":"E Jutten, L C L T van Kempen, G F H Diercks, B L van Leeuwen, S Kruijff, K P Wevers","doi":"10.1007/s40291-024-00764-4","DOIUrl":"https://doi.org/10.1007/s40291-024-00764-4","url":null,"abstract":"<p><strong>Introduction: </strong>Anorectal melanoma is a rare neoplasm with an aggressive behavior and poor prognosis. Recently, recurrent gene mutations related to anorectal melanoma have been identified in a small series of cases, and this holds promise for targeted therapies, analogous to cutaneous melanoma. The purpose of this study was to analyze testing rates and prevalence of mutations in anorectal melanoma in the Dutch population.</p><p><strong>Methods: </strong>The Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank were queried for all patients with a diagnosis of anorectal melanoma (2009-2019) and for whom a molecular analysis was performed. The genes that were tested and mutations that were reported were recorded. Mutation status was correlated with clinical characteristics.</p><p><strong>Results: </strong>In the period 2009-2019, 121 patients were diagnosed with anorectal melanoma. A molecular analysis was performed for 81 (67%) using single gene testing and various next-generation sequencing panels. Testing rates increased from 53% in 2009-2012 to 73% in 2016-2019. In 29/81 (36%) analyzed tumors, one or more mutations were reported: mutations in KIT (16/70, 23%), CTNNB1 (3/20, 15%), NRAS (6/60, 10%), BRAF non-V600E (4/74, 5%), GNAS (1/19, 5%), KRAS (1/28, 4%), BRAF V600E (1/74, 1%), and SF3B1 (1/1). In this cohort, a positive correlation was found between BRAF mutation status and age. Mutation status did not correlate with sex, date of diagnosis, tumor stage or surgical treatment. Survival was not influenced by any mutation status.</p><p><strong>Conclusion: </strong>KIT was the most frequently mutated gene in the 81 analyzed anorectal melanomas in the period 2009-2019. With the increasing testing rates and use of next generation sequencing, the molecular landscape of anorectal melanomas is gradually being revealed. Adoption of broad mutation analysis will reveal potentially actionable targets for treatment of patients with anorectal melanoma.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911102","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}