Circulating Tumour DNA Is a Biomarker of Response in Angioimmunoblastic T-Cell Lymphoma

Yannakou, CK; Wu, S; Rajah, K; Abeyakoon, C; Nguyen-Ngo, C; Yap, YZ; Sheldon, J; Blombery, P; Prince, HM

Author(s): Yannakou, CK; Wu, S; Rajah, K; Abeyakoon, C; Nguyen-Ngo, C; Yap, YZ; Sheldon, J; Blombery, P; Prince, HM;
Details: Publication Year 2025-07-13,Volume 26,Issue #14,Page 6719
Journal Title: International Journal of Molecular Sciences
Publication Type: Research article
Abstract: 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.
Publisher: MDPI
Keywords: Humans; *Circulating Tumor DNA/blood/genetics; Female; Male; *Biomarkers, Tumor/genetics/blood; Aged; Middle Aged; *Immunoblastic Lymphadenopathy/genetics/blood; Mutation; DNA Methyltransferase 3A; *Lymphoma, T-Cell/genetics/blood/drug therapy; Dioxygenases/genetics; Isocitrate Dehydrogenase/genetics; rhoA GTP-Binding Protein/genetics; DNA-Binding Proteins/genetics; Proto-Oncogene Proteins/genetics; Aged, 80 and over; DNA (Cytosine-5-)-Methyltransferases/genetics; Adult; angioimmunoblastic T-cell lymphoma; circulating tumour DNA; measurable residual disease
Department(s): Pathology; Haematology
Publisher's Version: https://doi.org/10.3390/ijms26146719
Open Access at Publisher's Site: https://doi.org/10.3390/ijms26146719
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-08-28 11:09:28

Last Modified: 2025-08-28 11:09:36