{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:39:12Z","timestamp":1763552352465,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,13]],"date-time":"2025-07-13T00:00:00Z","timestamp":1752364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Epworth Medical Foundation"},{"name":"the Snowdome Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms26146719","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:45:52Z","timestamp":1752572752000},"page":"6719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Circulating Tumour DNA Is a Biomarker of Response in Angioimmunoblastic T-Cell Lymphoma"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-2034","authenticated-orcid":false,"given":"Costas Kleanthes","family":"Yannakou","sequence":"first","affiliation":[{"name":"Epworth HealthCare, Melbourne 3002, Australia"},{"name":"Department of Clinical Pathology, The University of Melbourne, Melbourne 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8339-7343","authenticated-orcid":false,"given":"Simon","family":"Wu","sequence":"additional","affiliation":[{"name":"Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne 3010, Australia"},{"name":"Peter MacCallum Cancer Centre, Melbourne 3000, Australia"},{"name":"Dorevitch Pathology, Melbourne 3084, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karthik","family":"Rajah","sequence":"additional","affiliation":[{"name":"QML Pathology, Brisbane 4172, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8848-9423","authenticated-orcid":false,"given":"Chathuri","family":"Abeyakoon","sequence":"additional","affiliation":[{"name":"Epworth HealthCare, Melbourne 3002, Australia"},{"name":"Monash Health, Melbourne 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlyn","family":"Nguyen-Ngo","sequence":"additional","affiliation":[{"name":"Epworth HealthCare, Melbourne 3002, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan Zhuang","family":"Yap","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre, Melbourne 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Sheldon","sequence":"additional","affiliation":[{"name":"Epworth HealthCare, Melbourne 3002, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piers","family":"Blombery","sequence":"additional","affiliation":[{"name":"Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne 3010, Australia"},{"name":"Peter MacCallum Cancer Centre, Melbourne 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-2448","authenticated-orcid":false,"given":"Henry Miles","family":"Prince","sequence":"additional","affiliation":[{"name":"Epworth HealthCare, Melbourne 3002, Australia"},{"name":"Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e361","DOI":"10.3324\/haematol.2015.126300","article-title":"Angioimmunoblastic T-cell lymphoma is the most common T-cell lymphoma in two distinct French information data sets","volume":"100","author":"Parrens","year":"2015","journal-title":"Haematologica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/annonc\/mdf033","article-title":"Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): Results from the Non-Hodgkin\u2019s Lymphoma Classification Project","volume":"13","author":"Weisenburger","year":"2002","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1182\/blood.2020010387","article-title":"Outcomes and prognostic factors in angioimmunoblastic T-cell lymphoma: Final report from the international T-cell Project","volume":"138","author":"Advani","year":"2021","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1002\/ajh.24128","article-title":"Utility of interim and end-of-treatment PET\/CT in peripheral T-cell lymphomas: A review of 124 patients","volume":"90","author":"Pedersen","year":"2015","journal-title":"Am. J. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1002\/cncr.22807","article-title":"The usefulness of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and a comparison of 18F-FDG-pet with 67gallium scintigraphy in the evaluation of lymphoma","volume":"110","author":"Tsukamoto","year":"2007","journal-title":"Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"285","DOI":"10.6004\/jnccn.2022.0015","article-title":"T-Cell Lymphomas, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology","volume":"20","author":"Horwitz","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1038\/s41375-022-01618-w","article-title":"Circulating tumor DNA in B-cell lymphoma: Technical advances, clinical applications, and perspectives for translational research","volume":"36","author":"Lauer","year":"2022","journal-title":"Leukemia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1200\/JCO.2018.78.5246","article-title":"Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma","volume":"36","author":"Kurtz","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41375-019-0541-6","article-title":"Genotyping circulating tumor DNA of pediatric Hodgkin lymphoma","volume":"34","author":"Desch","year":"2020","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"291","DOI":"10.4143\/crt.2022.017","article-title":"Circulating Tumor DNA-Based Genotyping and Monitoring for Predicting Disease Relapses of Patients with Peripheral T-Cell Lymphomas","volume":"55","author":"Kim","year":"2023","journal-title":"Cancer Res. Treat"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/ng.2873","article-title":"Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas","volume":"46","author":"Palomero","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1182\/blood-2011-11-391748","article-title":"IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma","volume":"119","author":"Cairns","year":"2012","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/ng.2872","article-title":"Somatic RHOA mutation in angioimmunoblastic T cell lymphoma","volume":"46","author":"Enami","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/ng.2916","article-title":"A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma","volume":"46","author":"Yoo","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1182\/blood-2013-10-531509","article-title":"A targeted mutational landscape of angioimmunoblastic T-cell lymphoma","volume":"123","author":"Odejide","year":"2014","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1111\/bjh.19089","article-title":"Angioimmunoblastic T-cell lymphoma: Novel recurrent mutations and prognostic biomarkers by cell-free DNA profiling","volume":"203","author":"Zhang","year":"2023","journal-title":"Br. J. Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15084","DOI":"10.1073\/pnas.1617929114","article-title":"The IDH2 R172K mutation associated with angioimmunoblastic T-cell lymphoma produces 2HG in T cells and impacts lymphoid development","volume":"113","author":"Lemonnier","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1182\/blood-2016-02-698977","article-title":"Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell\u2013derived lymphomas","volume":"128","author":"Vallois","year":"2016","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3324\/haematol.2020.265991","article-title":"Early detection of T-cell lymphoma with T follicular helper phenotype by RHOA mutation analysis","volume":"107","author":"Dobson","year":"2022","journal-title":"Haematologica"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1056\/NEJMoa1409405","article-title":"Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence","volume":"371","author":"Genovese","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1056\/NEJMoa1408617","article-title":"Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes","volume":"371","author":"Jaiswal","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/hon.2319","article-title":"Response to 5-azacytidine in a patient with TET2-mutated angioimmunoblastic T-cell lymphoma and chronic myelomonocytic leukaemia preceded by an EBV-positive large B-cell lymphoma","volume":"35","author":"Saillard","year":"2017","journal-title":"Hematol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1007\/s00277-017-3038-2","article-title":"Detection of the circulating tumor DNAs in angioimmunoblastic T- cell lymphoma","volume":"96","author":"Komori","year":"2017","journal-title":"Ann. Hematol."},{"key":"ref_24","first-page":"4198","article-title":"Next-generation sequencing\u2013based monitoring of circulating tumor DNA reveals clonotypic heterogeneity in untreated PTCL","volume":"5","author":"Miljkovic","year":"2021","journal-title":"Blood Adv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ccell.2018.01.001","article-title":"RHOA G17V Induces T Follicular Helper Cell Specification and Promotes Lymphomagenesis","volume":"33","author":"Cortes","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/path.5376","article-title":"Angioimmunoblastic T-cell lymphoma contains multiple clonal T-cell populations derived from a common TET2 mutant progenitor cell","volume":"250","author":"Yao","year":"2020","journal-title":"J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e516","DOI":"10.1038\/bcj.2016.122","article-title":"Identification of cell-type-specific mutations in nodal T-cell lymphomas","volume":"7","author":"Nguyen","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1182\/blood-2017-11-818617","article-title":"RhoA G17V is sufficient to induce autoimmunity and promotes T-cell lymphomagenesis in mice","volume":"132","author":"Ng","year":"2018","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2134536","DOI":"10.1080\/2162402X.2022.2134536","article-title":"RHOA G17V induces T follicular helper cell specification and involves angioimmunoblastic T-cell lymphoma via upregulating the expression of PON2 through an NF-\u03baB-dependent mechanism","volume":"11","author":"Que","year":"2022","journal-title":"OncoImmunology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.ccell.2023.01.003","article-title":"IDH2 and TET2 mutations synergize to modulate T Follicular Helper cell functional interaction with the AITL microenvironment","volume":"41","author":"Leca","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5588","DOI":"10.1182\/bloodadvances.2021005171","article-title":"Peripheral T-cell lymphoma: Molecular profiling recognizes subclasses and identifies prognostic markers","volume":"5","author":"Cereceda","year":"2021","journal-title":"Blood Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1056\/NEJMc1806413","article-title":"High-Risk Clonal Hematopoiesis as the Origin of AITL and NPM1-Mutated AML","volume":"379","author":"Tiacci","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/jha2.354","article-title":"T-cell lymphoma, B-cell lymphoma, and myelodysplastic syndrome harboring common mutations: Trilineage tumorigenesis from a common founder clone","volume":"3","author":"Yoshihara","year":"2022","journal-title":"eJHaem"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1182\/bloodadvances.2020001636","article-title":"Clonal hematopoiesis in angioimmunoblastic T-cell lymphoma with divergent evolution to myeloid neoplasms","volume":"4","author":"Lewis","year":"2020","journal-title":"Blood Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1111\/j.1365-2141.2007.06725.x","article-title":"Frequent occurrence of B-cell lymphomas in angioimmunoblastic T-cell lymphoma and proliferation of Epstein\u2013Barr virus-infected cells in early cases","volume":"138","author":"Willenbrock","year":"2007","journal-title":"Br. J. Haematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1200\/JCO.2013.54.8800","article-title":"Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification","volume":"32","author":"Cheson","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13073-017-0427-z","article-title":"PathOS: A decision support system for reporting high throughput sequencing of cancers in clinical diagnostic laboratories","volume":"9","author":"Doig","year":"2017","journal-title":"Genome Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative genomics viewer","volume":"29","author":"Robinson","year":"2011","journal-title":"Nat. Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6719\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:09:19Z","timestamp":1760033359000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,13]]},"references-count":38,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26146719"],"URL":"https:\/\/doi.org\/10.3390\/ijms26146719","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,7,13]]}}}