Identification of genetic subtypes in follicular lymphoma.

Humans Lymphoma, Follicular / genetics Female Male Mutation Middle Aged Aged Biomarkers, Tumor / genetics Prognosis

Journal

Blood cancer journal

ISSN: 2044-5385

Titre abrégé: Blood Cancer J

Pays: United States

ID NLM: 101568469

Informations de publication

Date de publication:
07 Aug 2024

Historique:

received: 28 02 2024

accepted: 24 07 2024

revised: 17 07 2024

medline: 8 8 2024

pubmed: 8 8 2024

entrez: 7 8 2024

Statut: epublish

Résumé

Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes in 713 pre-treatment tumor tissue samples. Our analysis revealed the existence of five subtypes with unique genetic profiles that correlated with clinicopathological characteristics. The clusters were enriched in specific mutations as follows: CS (CREBBP and STAT6), TT (TNFAIP3 and TP53), GM (GNA13 and MEF2B), Q (quiescent, for low mutation burden), and AR (mutations of mTOR pathway-related genes). The subtype Q was enriched for patients with stage I disease and associated with a lower proliferative history than the other subtypes. The AR subtype was unique in its enrichment for IgM-expressing FL cases and was associated with advanced-stage and more than 4 nodal sites. The existence of subtypes was validated in an independent cohort of 418 samples from the GALLIUM trial. Notably, patients assigned to the TT subtype consistently experienced inferior progression-free survival when treated with immunochemotherapy. Our findings offer insight into core pathways distinctly linked with each FL cluster and are expected to be informative in the era of targeted therapies.

Identifiants

DOI: 10.1038/s41408-024-01111-w PMID: 39112453

pubmed: 39112453

doi: 10.1038/s41408-024-01111-w

pii: 10.1038/s41408-024-01111-w

doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

128

Subventions

Organisme : Terry Fox Research Institute (Institut de Recherche Terry Fox)

ID : 1079

Organisme : Leukemia and Lymphoma Society (Leukemia & Lymphoma Society)

ID : 6599-20

Organisme : Leukemia and Lymphoma Society of Canada (Leukemia & Lymphoma Society of Canada)

ID : 513421

Organisme : Else Kröner-Fresenius-Stiftung (Else Kroner-Fresenius Foundation)

ID : 2021_EKES.13

Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)

ID : WE 4679/2

Informations de copyright

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