Clinical implications of circulating tumor DNA in classical Hodgkin lymphoma
- Pirosa, Maria Cristina
- Rossi, Davide (Degree supervisor)
- 2025
PhD: Università della Svizzera italiana
English
In this study, we used an optimized 344-kb CAPP-seq panel to analyze circulating tumor DNA (ctDNA) from 297 patients, generating an integrated map of coding and non-coding alterations in classical Hodgkin Lymphoma (cHL). Non-coding regulatory mutations were widespread, affecting 86% of patients, mirroring patterns observed in diffuse large B-cell lymphoma. Among these, a recurrent somatic expression quantitative trait locus (seQTL) involving BCL6 was identified in 30% of cases. This lesion overlapped with regions of accessible chromatin and increased H3K27 acetylation, disrupted PRDM1 binding, and correlated with BCL6 expression in cHL cells. Consistent with this, weak to strong BCL6 protein expression was detected in 68% of cases, and its transcriptional repression program resembled that of germinal center B cells. Pharmacologic degradation of BCL6 led to derepression of its direct target genes and impaired cellular proliferation. These findings expand the understanding of oncogenic mechanisms in cHL and identify BCL6 as a biological vulnerability and a potential therapeutic target in a subset of patients. Neoantigen burden and, importantly, neoantigen clonality were associated with tumor microenvironment features and predicted response to immune checkpoint blockade. Finally, the study indicates that ctDNA analysis may help resolve ambiguous post-treatment PET/CT–positive findings by distinguishing true residual disease from inflammatory uptake.
- Collections
- Language
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- English
- Classification
- Medicine
- License
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License undefined
- Open access status
- green
- Identifiers
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- NDP-USI 2025BIOMED009
- ARK ark:/12658/srd1336636
- URN urn:nbn:ch:rero-006-124219
- Persistent URL
- https://n2t.net/ark:/12658/srd1336636
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