Search Results (129)

Circulating tumour DNA (ctDNA) assays are increasingly applied in haematological malignancies for non-invasive genotyping, quantitative response assessment, measurable residual disease (MRD) detection, and relapse surveillance, often complementing bone marrow-based testing and, in selected scenarios, potentially reducing its frequency. Yet, translating ctDNA results into comparable clinical decisions across laboratories, platforms, and time remains challenging because ctDNA measurements are influenced by the definition of the measurand (for example, variant allele fraction versus mutant molecules per mL), pre-analytical variables, end-to-end workflow losses, and lineage-specific confounders such as clonal haematopoiesis of indeterminate potential (CHIP), therapy-related clonal haematopoiesis, and compartmental disease (marrow, plasma, cerebrospinal fluid, extramedullary sites). This review proposes a harmonisation framework for haematological ctDNA based on three linked concepts—metrological traceability, which connects reported values to reference systems with stated uncertainty, commutability, which ensures that reference materials behave like patient specimens across diverse workflows and fit-for-purpose reference materials that support calibration, and quality control, external quality assessment, and cut-off setting for intended uses such as early molecular response in large B-cell lymphoma, molecular MRD in acute myeloid leukaemia, and deep response monitoring in multiple myeloma. This framework is accompanied by harmonised CHIP-aware reporting rules for settings without matched cellular DNA and practical change-control/bridging strategies to preserve clinical decision thresholds when platforms or bioinformatic pipelines evolve. Full article

Background: Multiple myeloma (MM) is characterised by clonal expansion of plasma cells (PCs) in the bone marrow (BM). Disease assessment and monitoring typically rely on invasive, single-site procedures, such as BM biopsies (BMBs), which may inadequately capture intra- and extra-medullary spatial heterogeneity. Circulating plasma cells (CPCs), enriched from peripheral blood (PB), may represent a minimally invasive alternative or adjunct for molecular profiling. Objectives: This study aimed to evaluate the feasibility of using CPCs, enriched from PB, for mRNA analysis in plasma cell dyscrasia, including MM. A secondary objective was to assess whether mRNA expression levels of the endoplasmic reticulum (ER) stress sensors X-box-binding protein 1 (uXBP1) and activating transcription factor 6 (ATF6), and the chaperone-mediated autophagy marker Lysosomal-Associated Membrane Protein 2 (LAMP2A) by droplet digital PCR (ddPCR), were associated with resistance to the second-generation proteasome inhibitor (PI) carfilzomib (Cfz). Methods: Multiple myeloma (MM) cell lines (H929 and U266) and their carfilzomib-adapted derivatives were used to establish and validate droplet digital PCR (ddPCR) assays targeting ER stress (uXBP1, ATF6) and autophagy-related (LAMP2A) transcripts. Solid tumour cell lines, including serum-starved HeLa cells, served as biological controls to support assay specificity and sensitivity. Total RNA was extracted and reverse-transcribed to complementary DNA prior to analysis. Transcript levels were normalised to those of β-actin or GAPDH, as appropriate. ddPCR was performed using the BioRad QX200 system, with results reported as the normalised transcript copy number per microlitre of reaction. Matched bone marrow aspirate (BMA) and peripheral blood (PB) samples were collected at a single clinical time point from adults undergoing investigation for plasma cell dyscrasia between January 2021 and December 2023. Samples were obtained as part of standard clinical care and/or during treatment with Bortezomib (Btz) or Cfz. Mononuclear cells were isolated by density gradient centrifugation, and CD138⁺ plasma cells were enriched by fluorescence-activated cell sorting. Enrichment purity was assessed qualitatively by immunofluorescence microscopy using CD138 and CD117 markers. Samples yielding fewer than 1000 CD138⁺ plasma cells were excluded, resulting in 10 evaluable matched patient pairs. Results: Carfilzomib-adapted MM cell lines demonstrated reduced levels of uXBP1, ATF6, and LAMP2A mRNA compared to treatment-naïve cells. In matched BM and PB samples, uXBP1 mRNA levels were consistently lower in circulating PCs than in BM-derived PCs, whereas ATF6 mRNA levels were concordant between compartments. LAMP2A mRNA levels exhibited marked inter-patient heterogeneity. Conclusions: This study demonstrates the feasibility of using CPCs as a minimally invasive source for mRNA-based biomarker assessment and highlights ddPCR as a sensitive platform for quantifying ER stress and chaperone-mediated autophagy related transcripts in CPCs. Cfz adaptation was associated with reduced levels of uXBP1 and LAMP2A mRNA in MM cell lines. Future prospective studies evaluating the clinical utility of ER stress and chaperone-mediated autophagy associated transcripts in CPCs as predictors of resistance to PI are warranted. Full article

Soft-tissue sarcomas (STSs) comprise a rare, heterogeneous group of mesenchymal malignancies in which histologic grade remains the strongest determinant of outcome, metastatic risk, and therapeutic strategy. Intermediate/high-grade STSs exhibit a pronounced propensity for early distant relapse, yet growing evidence indicates that metastatic behaviour is not uniform. Within this spectrum, an oligometastatic phenotype, characterised by a limited number of metastases, often confined to the lung, has emerged as a clinically and biologically distinct state associated with more indolent metastatic kinetics and improved survival when treated with aggressive local interventions. However, the criteria that define true oligometastatic STSs remain unsettled, and prospective evidence is lacking. Emerging molecular and immunological correlates provide a potential framework for biological triage. Low genomic complexity (low-risk CINSARC), a B-cell/TLS-rich tumour microenvironment, high immune-cytotoxic signatures, and persistently low or undetectable circulating tumour DNA (ctDNA) are each linked to reduced metastatic competence and may underpin oligometastatic trajectories. Conversely, high chromosomal instability, immunosuppressive microenvironments, and elevated ctDNA levels align with covertly polymetastatic biology despite limited radiographic disease. In this context, artificial intelligence and machinelearning approaches applied to computational genomics, immune profiling, imaging, and liquid-biopsy data offer a powerful strategy to integrate these multi-dimensional features and refine predictions of metastatic behaviour in STS. Oligometastatic STS therefore represents a biologically definable subset amenable to multimodal management integrating local ablative therapies, systemic agents, and immune-based strategies. Prospective, biomarker-stratified trials are needed to validate selection frameworks and optimise treatment sequencing in this evolving therapeutic space. Full article

Cancer is a heterogeneous systemic disease that is strongly influenced by dynamic interactions with the tumour microenvironment (TME). Despite major advances in understanding spatial and molecular tumour heterogeneity, the temporal dynamics of tumours have received far less attention. Growing evidence has linked circadian clocks to cancer risk, progression, and treatment response, including in breast cancer. However, temporal regulation has yet to be recognized as a cancer hallmark, and its interaction with the TME remains poorly understood. This review examines how circadian rhythms organize breast cancer biology through bidirectional interactions with the TME. Circadian clocks coordinate proliferation, DNA damage responses, metabolism, and immune surveillance. Ageing, chronic stress, and obesity, all of which are established breast cancer risk modifiers, disrupt these rhythms and are reciprocally exacerbated by circadian dysfunction, establishing feed-forward loops that accelerate disease. Within the TME, the extracellular matrix (ECM) plays a central role in mediating this bidirectional control. Stiffened fibrotic stroma dampens epithelial clock amplitude, while circadian rhythms in turn shape collagen turnover and ECM remodelling. These dynamics can foster inflammation, stem cell expansion, and metastatic dissemination, including time-of-day-dependent release of circulating breast tumour cells. Systemically, circadian clocks gate immune cell trafficking, creating predictable windows of immunosurveillance and therapeutic vulnerability. By integrating insights from mechanobiology, metabolism, immune regulation, and ageing, we position circadian timing as a unifying layer that connects cell-intrinsic programmes with the evolving breast TME. Understanding these connections opens new opportunities for chronotherapeutic strategies in which treatment timing is aligned with circadian rhythms to improve outcomes. Full article

Introduction: Neoadjuvant systemic and immunotherapy strategies in non-metastatic colon cancer have demonstrated high pathological response rates, raising interest in surgery-sparing approaches. Circulating tumour DNA (ctDNA) is an emerging biomarker for treatment response and minimal residual disease, but its role in guiding surgical omission in colon cancer remains unclear. This systematic review evaluates the diagnostic and prognostic accuracy of ctDNA in predicting pathological response following neoadjuvant therapy in non-metastatic colon cancer. Methods: A systematic review was conducted in accordance with PRISMA guidelines. PubMed, Embase/MEDLINE, Scopus, and the Cochrane Register were searched from inception to 21 October 2025. Eligible studies included adults with non-metastatic colon cancer treated with neoadjuvant therapy who had serial ctDNA assessment prior to surgery. Results: Three cohort studies comprising 100 patients met inclusion criteria. Baseline ctDNA detection ranged from 42% to 84%. Across studies, ctDNA clearance following neoadjuvant therapy was consistently associated with major pathological response or pathological complete response, whereas persistent ctDNA strongly predicted residual viable tumour at resection. In the largest prospective cohort, 5 of 26 patients (19%) achieved ctDNA clearance prior to surgery; all were pathological responders, while 19 of 26 patients (73%) with persistent ctDNA demonstrated no pathological response. No study reported pathological complete response in the presence of persistently positive ctDNA. No prospective trial formally evaluated ctDNA-guided surgical omission. Conclusions: Current evidence does not support the use of ctDNA alone to guide omission of surgery after neoadjuvant therapy in non-metastatic colon cancer—even in patients who show complete pathological response. While persistent ctDNA reliably identifies patients with residual disease, ctDNA clearance lacks sufficient positive predictive value to safely forego surgery. Prospective trials with standardised ctDNA platforms and predefined non-operative management protocols are required before ctDNA-guided organ preservation can be recommended. Full article

Background and Objectives: Melanoma is an aggressive cutaneous malignancy with a high recurrence rate even after complete resection. Circulating tumour DNA (ctDNA) has emerged as a promising biomarker for detecting minimal residual disease (MRD), assessing tumour burden, and predicting recurrence. This study aims to evaluate the clinical utility of ctDNA analysis in determining completeness of melanoma resection and disease staging. Materials and Methods: A systematic review was conducted in accordance with PRISMA guidelines, searching PubMed and Web of Science for studies published between January 2017 and February 2025. Eligible studies assessed ctDNA before, during, or after melanoma resection to evaluate surgical completeness and staging. Studies without perioperative ctDNA assessment or which focused solely on immunotherapy efficacy were excluded. Results: Fourteen studies with 1077 patients met the inclusion criteria. Preoperative ctDNA detection correlated with advanced stage, greater tumour burden, and poorer survival. Postoperative ctDNA persistence was strongly associated with recurrence, often detectable months before clinical relapse. In most patients remaining disease-free, ctDNA cleared within weeks after surgery. ctDNA levels reflected metastatic spread, though sensitivity was lower for brain lesions. Across studies, undetectable postoperative ctDNA was consistently linked to longer recurrence-free survival. Conclusions: Perioperative ctDNA analysis shows promise as a prognostic biomarker for detecting residual disease and anticipating relapse in melanoma. However, heterogeneity in patient cohorts, study design, and ctDNA detection methods limits immediate clinical application. Large, standardized prospective trials are needed to validate ctDNA for perioperative management. Full article

Ocular melanomas, comprising uveal melanoma (UM) and conjunctival melanoma (CoM), represent the most common primary intraocular and ocular surface malignancies in adults. Although rare compared with cutaneous melanoma, they exhibit unique molecular landscapes that provide critical opportunities for biomarker-driven precision medicine. In UM, recurrent mutations in GNAQ and GNA11, together with alterations in BAP1, SF3B1, and EIF1AX, have emerged as key prognostic biomarkers that stratify metastatic risk and guide surveillance strategies. Conversely, in CoM, the mutational spectrum overlaps with cutaneous melanoma, with frequent alterations in BRAF, NRAS, NF1, and KIT, offering actionable targets for personalised treatment. Beyond genomics, epigenetic signatures, microRNAs, and protein-based markers provide further insights into tumour progression, microenvironmental remodelling, and immune evasion. In parallel, liquid biopsy has emerged as a minimally invasive approach for real-time disease monitoring. Analyses of circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and exosome-derived microRNAs demonstrate increasing potential for early detection of minimal residual disease, prognostic assessment, and evaluation of treatment response. However, the clinical integration of these biomarkers remains limited by tumour heterogeneity, technical variability, and the lack of unified translational frameworks. This review synthesises current knowledge of molecular and liquid biopsy biomarkers in ocular melanoma, highlighting their relevance for diagnosis, prognosis, and treatment personalisation. The integration of established tissue-based molecular markers with novel liquid biopsy technologies will enable a unique framework for biomarker-guided precision oncology and risk-adapted surveillance in uveal and conjunctival melanoma, offering insight into strategies for early detection, therapeutic monitoring, and personalised clinical management. Full article

The escalating incidence of colorectal cancer (CRC), particularly the alarming rise in early-onset cases, necessitates a paradigm shift from a purely genetic perspective to a broader investigation of promising pathways. This review explores the “nutri-epigenetic” interface, positioning liquid biopsy as a critical technology for translating dietary impacts into actionable clinical biomarkers. We contrast the molecular consequences of the Western dietary pattern, characterized by methyl-donor deficiency and pro-inflammatory metabolites, with the protective mechanisms of the Mediterranean diet. Mechanistically, we detail how Western-style diets drive a specific “epigenetic double-hit”: promoting global DNA hypomethylation (destabilizing LINE-1) while paradoxically inducing promoter hypermethylation of critical tumour suppressors (MLH1, APC, MGMT) and silencing tumour-suppressive microRNAs (miR-34b/c, miR-137) via methylation of their encoding genes. Conversely, we highlight the capacity of Mediterranean bioactive compounds (e.g., resveratrol, curcumin, butyrate) to inhibit DNA methyltransferases and restore epigenetic homeostasis. Bridging molecular biology and clinical utility, we demonstrate how these diet-sensitive signatures, specifically circulating methylated DNA and dysregulated microRNAs, can be captured via liquid biopsy. We propose that these circulating analytes serve as dynamic, accessible biomarkers for monitoring the molecular progression toward a carcinogenic state, thereby establishing a novel framework for personalized risk stratification and validating the efficacy of preventive nutritional strategies. Full article

Background: Oligometastatic bladder cancer (OMBC) is increasingly recognised as an intermediate state between localised and widespread metastatic disease, although its definition and optimal management remain uncertain. Patients with OMBC have a generally more favourable prognosis compared to patients with metastatic disease. However, its definition, diagnostic criteria, and optimal management remain poorly standardised. Methods: This narrative review summarises current evidence on the definitions, diagnostic approaches, and treatment strategies for OMBC, with an emphasis on emerging biological and molecular insights that may refine disease classification and guide therapy. Results: Existing definitions of OMBC rely on lesion count and anatomical distribution, overlooking molecular and clinicopathological heterogeneity that influences prognosis and treatment response. Advances in Positron Emission Tomography (PET)/Computed Tomography (CT) and magnetic resonance imaging (MRI) have improved detection of small-volume disease, while liquid biopsy and circulating tumour DNA show promise for assessing micrometastatic burden. Therapeutic approaches, including metastasis-directed and consolidative therapies, are under investigation. Nonetheless, most data are derived from small, retrospective series, and evidence from prospective studies remains limited. Conclusions: Prospective, biomarker-integrated, and randomised trials are essential to refine definitions, optimise patient selection for therapy, and define the role of precision-based multimodal therapy in OMBC management. Full article

Cutibacterium acnes (C. acnes) has emerged as a potential contributor to prostate cancer (PCa) pathogenesis, yet the mechanistic basis remains unclear. This review explores the prevalence, persistence and mechanistic impact of C. acnes within the prostate to help decipher the functional consequence and diagnostic value of a C. acnes infection in this setting. We examine the evidence supporting C. acnes colonisation of both premalignant and malignant tissue, and critically evaluate how prostate tumour physiology, particularly hypoxia and low pH, may facilitate microbial persistence. Emerging data suggest that C. acnes modulates inflammatory and immune pathways, influencing macrophage activation, cytokine production, and the regulation of immune checkpoints. Additionally, we discuss studies demonstrating its involvement in DNA damage, host cell metabolism, and extracellular matrix remodelling. The identification of C. acnes in urinary and gut microbiomes, alongside the presence of its genomic DNA in extracellular vesicles in circulation indicate broad diagnostic potential. While discrepancies in methodology have hampered a consensus, recent genomic and functional studies provide new avenues to distinguish contamination from true pathogenicity. Ultimately, future research exploring whether C. acnes is a biomarker, bystander, or bona fide driver of PCa, and its potential role in personalised diagnostics are crucial to advance the field and unravel the predictive and therapeutic value of C. acnes. Clarifying this relationship will advance our understanding of microbiome-cancer dynamics and could help inform innovative early detection and screening strategies that improve patient care. Full article

Background: Metastatic prostate cancers frequently harbour pathogenic aberrations in Homologous Recombination Repair (HRR) genes that confer sensitivity to PARP inhibitors (PARPi). Therefore, accurate identification of all eligible patients is needed. The development of a circulating tumour DNA (ctDNA) testing alternative is promising as genomic testing of archived tissue leads to a failure rate of up to 30–40% in prostate cancer. Methods: This was a bi-institutional retrospective cohort study of patients with metastatic prostate cancer treated at the Jewish General Hospital or the McGill University Health Center, Montreal, Canada, between 2021 and 2023. Molecular data and treatment information were abstracted from a chart review. Chi-square, Fisher’s exact test, and Mann–Whitney tests were used to assess differences between groups. Results: We identified 484 metastatic prostate cancer patients. Somatic and germline testing for HRR was performed in 55.4% (n = 268) and 20% (n = 97) patients, respectively. Somatic testing was performed on tissue (n = 192, 71.6%) or ctDNA from liquid biopsies (n = 18, 6.7%) or both (n = 58, 21.7%). Pathogenic somatic HRR alterations were detected in 48 patients (17.9%). BRCA2 was the most frequent (n = 17), followed by ATM (n = 11), then CHEK2 (n = 5). Amongst patients with germline testing, 13/97 (13.4%) had pathogenic alterations predicted to lead to deficient HRR, mostly BRCA2 (n = 9), and three had detectable BRCA2 in tissue. Dual testing modality (tissue+ctDNA) significantly enhanced the detection rate of HRR alterations 19/58 (32.7%) vs. 29/210 (13.8%) for single testing modality (tissue or ctDNA), p = 0.008. The rate of inconclusive results was significantly lower in dual testing modality 0/58 (0%) vs. 25/210 in single testing modality (11.9%), p = 0.003. Amongst the 14 patients who had discordant results between liquid and tissue tests, HRR abnormalities were more frequently identified in ctDNA (n = 11) vs. tissue (n = 3). Patients who had HRR deficiency detected only in ctDNA had older tissue samples (median 5.6 years) compared to those who had deficient HRR detected only in tissue (median 0.2 years; p = 0.14). Conclusions: These data highlight a potential role in implementing liquid biopsy—especially in patients who only have older archival tissue available or failed tissue testing—to improve the detection rate of deficient HRR. Our ongoing prospective study will further validate whether the addition of liquid biopsy can identify more patients who are eligible to receive precision therapies by increasing the rate of detection of HRR deficiency compared to routine tissue testing alone. Full article

Breast cancer is the most common malignancy and leading cause of cancer-related mortality among women worldwide. Oestrogen receptor (ER)-positive disease accounts for the majority of cases, where endocrine and targeted therapies have substantially improved survival. Nevertheless, resistance to therapy remains inevitable, emphasising the need for precision strategies informed by molecular profiling. The molecular landscape of ER-positive breast cancer is increasingly complex, characterised by diverse genomic alterations driving resistance and progression. Advances in next-generation sequencing and circulating tumour DNA (ctDNA) technologies enable the dynamic assessment of tumour heterogeneity and clonal evolution, informing prognostication and guiding biomarker-driven therapy. Uniquely, this review integrates molecular phenotyping with clinical treatment algorithms for advanced ER-positive breast cancer, providing a practical framework to translate genomic insights into patient care. Key genomic alterations and targeted strategies with demonstrated clinical benefit, including oral selective ER degraders (SERDs) and PI3K/AKT/mTOR inhibitors in selected biomarker populations, are highlighted. Emerging targets, such as human epidermal growth factor 2 (HER2) mutations, and the potential of ctDNA monitoring to detect resistance and guide therapeutic escalation are also discussed. Incorporating molecular profiling, as recommended by international guidelines, into routine clinical decision making can personalise therapy and optimise patient outcomes. Addressing real-world challenges, including cost and accessibility, will be critical to achieving equitable implementation of precision oncology for patients with ER-positive breast cancer worldwide. Full article

Neuroblastoma (NB) is an aggressive childhood cancer requiring intensive multimodal therapies in high-risk (HRNB) patients. Currently, invasive surgical biopsies are required to classify NB risk group and assign treatment based on the tumour genetic profile. Circulating tumour DNA (ctDNA) obtained from blood samples can be used to identify tumour biomarkers. Here we applied targeted next-generation sequencing (tNGS) using a panel of 42 genes to analyse 32 NB ctDNA samples for the presence of single-nucleotide variants and copy number changes from 28 patients in all NB risk groups. In two additional ctDNA samples, droplet digital PCR was used to detect hotspot ALK variants. Pathogenic mutations with a variant allele frequency (VAF) > 1% were identified in 13/32 (41%) ctDNA samples. ALK and PTPN11 were the most frequent, each being detected in 4/32 (13%) samples, together with oncogene amplifications. Targeted NGS of ctDNA detected actionable variants, including those absent in the diagnostic primary tumour due to spatial and temporal heterogeneity. Our findings confirm the usefulness of ctDNA in detecting genetic abnormalities in NB. Full article

Background: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour, associated with poor survival outcomes and significant clinical challenges. Conventional diagnostic methods, including MRI, CT, and histopathological analysis of tissue biopsies, are limited by their inability to reliably distinguish treatment effects from true tumour progression, often resulting in misdiagnosis and delayed intervention. Repeated tissue biopsies are also invasive and unsuitable for longitudinal monitoring. Liquid biopsy, a minimally invasive approach analysing tumour-derived material in biofluids such as blood and cerebrospinal fluid (CSF), offers a promising alternative. This review aims to evaluate current evidence on circulating biomarkers including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), microRNAs (miRNAs), extracellular vesicles (EVs), and proteins in GBM diagnosis and monitoring, and to assess the potential role of artificial intelligence (AI) in enhancing their clinical application. Methods: A narrative synthesis of the literature was undertaken, focusing on studies that have investigated blood- and CSF-derived biomarkers in GBM patients. Key aspects evaluated included biomarker biology, detection techniques, diagnostic and prognostic value, current technical challenges, and progress towards clinical translation. Studies exploring AI and machine learning (ML) approaches for biomarker integration and analysis were also reviewed. Results: Liquid biopsy enables repeated and minimally invasive sampling of tumour-derived material, reflecting the genetic, epigenetic, proteomic, and metabolomic landscape of GBM. Although promising, its translation into routine clinical practice is hindered by the low abundance of circulating biomarkers and lack of standardised collection and analysis protocols. Evidence suggests that combining multiple biomarkers improves sensitivity and specificity compared with single-marker approaches. Emerging AI and ML tools show significant potential for improving biomarker discovery, integrating multi-omic datasets, and enhancing diagnostic and prognostic accuracy. Conclusions: Liquid biopsy represents a transformative tool for GBM management, with the capacity to overcome limitations of conventional diagnostics and provide real-time insights into tumour biology. By integrating multiple circulating biomarkers and leveraging AI-driven approaches, liquid biopsy could enhance diagnostic precision, enable dynamic disease monitoring, and improve clinical decision-making. However, large-scale validation and standardisation are required before routine clinical adoption can be achieved. Full article

Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive subtype of non-Hodgkin lymphoma, the monitoring of which is largely restricted to radiological methods. Diagnosis relies on identifying characteristic clinicopathological features, supported by the detection of recurrent somatic mutations in RHOA, TET2, IDH2 and DNMT3A. The characteristic molecular profile of AITL and the high levels of circulating tumour DNA (ctDNA) measurable in AITL before treatment makes this an attractive lymphoma subtype in which to further investigate the role of ctDNA monitoring. The detection of somatic mutations in pre-treatment AITL-containing tissue samples was compared to those detected in pre-treatment ctDNA samples in a cohort of 12 patients. Changes in ctDNA somatic mutation burden over time were then correlated with radiological response. All six paired pre-treatment ctDNA and tissue samples had variants in common. All (8/8) previously ctDNA-detectable IDH2 and RHOA variants were undetectable in ctDNA samples at the time of end-of-treatment complete metabolic response (CMR). In comparison, the majority of both previously ctDNA-detectable DNMT3A variants (3/4) and TET2 variants (6/11) were detectable in ctDNA samples at the time of end-of-treatment CMR. These observations suggest that IDH2/RHOA variants may be more reliable markers of measurable residual disease in AITL than DNMT3A/TET2 variants. Full article