Blood Cancer Journal (Aug 2024)
Identification of genetic subtypes in follicular lymphoma
- Victoria Shelton,
- Rajesh Detroja,
- Ting Liu,
- Keren Isaev,
- Anjali Silva,
- Verena Passerini,
- Mehran Bakhtiari,
- Lourdes Calvente,
- Michael Hong,
- Michael Y. He,
- Saloni Modi,
- Samantha A. Hershenfeld,
- Maja Ludvigsen,
- Charlotte Madsen,
- Stephen Hamilton-Dutoit,
- Francesco Annibale d’Amore,
- Marianne Brodtkorb,
- Nathalie A. Johnson,
- Tara Baetz,
- David LeBrun,
- Josh W. D. Tobin,
- Maher K. Gandhi,
- Andrew J. Mungall,
- Wei Xu,
- Susana Ben-Neriah,
- Christian Steidl,
- Jan Delabie,
- Rosemarie Tremblay-LeMay,
- Opeyemi Jegede,
- Oliver Weigert,
- Brad Kahl,
- Andrew M. Evens,
- Robert Kridel
Affiliations
- Victoria Shelton
- Princess Margaret Cancer Centre—University Health Network
- Rajesh Detroja
- Princess Margaret Cancer Centre—University Health Network
- Ting Liu
- Princess Margaret Cancer Centre—University Health Network
- Keren Isaev
- Princess Margaret Cancer Centre—University Health Network
- Anjali Silva
- Princess Margaret Cancer Centre—University Health Network
- Verena Passerini
- Department of Internal Medicine III, Ludwig-Maximilians-University (LMU) Hospital
- Mehran Bakhtiari
- Princess Margaret Cancer Centre—University Health Network
- Lourdes Calvente
- Princess Margaret Cancer Centre—University Health Network
- Michael Hong
- Princess Margaret Cancer Centre—University Health Network
- Michael Y. He
- Princess Margaret Cancer Centre—University Health Network
- Saloni Modi
- Princess Margaret Cancer Centre—University Health Network
- Samantha A. Hershenfeld
- Princess Margaret Cancer Centre—University Health Network
- Maja Ludvigsen
- Department of Clinical Medicine, Aarhus University
- Charlotte Madsen
- Department of Hematology, Aarhus University Hospital
- Stephen Hamilton-Dutoit
- Department of Pathology, Aarhus University Hospital
- Francesco Annibale d’Amore
- Department of Clinical Medicine, Aarhus University
- Marianne Brodtkorb
- Department of Oncology, Oslo University Hospital
- Nathalie A. Johnson
- Jewish General Hospital
- Tara Baetz
- Department of Oncology, Queen’s University
- David LeBrun
- Department of Pathology and Molecular Medicine, Queen’s University
- Josh W. D. Tobin
- Mater Research University of Queensland
- Maher K. Gandhi
- Mater Research University of Queensland
- Andrew J. Mungall
- Canada’s Michael Smith Genome Sciences Centre at BC Cancer
- Wei Xu
- Department of Biostatistics, Princess Margaret Cancer Centre, Dalla Lana School of Public Health, University of Toronto
- Susana Ben-Neriah
- BC Cancer
- Christian Steidl
- BC Cancer
- Jan Delabie
- Laboratory and Medicine Program, University Health Network
- Rosemarie Tremblay-LeMay
- Laboratory and Medicine Program, University Health Network
- Opeyemi Jegede
- Dana Farber Cancer Institute
- Oliver Weigert
- Department of Internal Medicine III, Ludwig-Maximilians-University (LMU) Hospital
- Brad Kahl
- Washington University
- Andrew M. Evens
- Rutgers Cancer Institute
- Robert Kridel
- Princess Margaret Cancer Centre—University Health Network
- DOI
- https://doi.org/10.1038/s41408-024-01111-w
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 13
Abstract
Abstract 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.
