Fiche publication
Date publication
janvier 2023
Journal
Nature medicine
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FEUGIER Pierre
,
Pr BROSEUS Julien
Tous les auteurs :
Parry EM, Leshchiner I, Guièze R, Johnson C, Tausch E, Parikh SA, Lemvigh C, Broséus J, Hergalant S, Messer C, Utro F, Levovitz C, Rhrissorrakrai K, Li L, Rosebrock D, Yin S, Deng S, Slowik K, Jacobs R, Huang T, Li S, Fell G, Redd R, Lin Z, Knisbacher BA, Livitz D, Schneider C, Ruthen N, Elagina L, Taylor-Weiner A, Persaud B, Martinez A, Fernandes SM, Purroy N, Anandappa AJ, Ma J, Hess J, Rassenti LZ, Kipps TJ, Jain N, Wierda W, Cymbalista F, Feugier P, Kay NE, Livak KJ, Danysh BP, Stewart C, Neuberg D, Davids MS, Brown JR, Parida L, Stilgenbauer S, Getz G, Wu CJ
Lien Pubmed
Résumé
Richter syndrome (RS) arising from chronic lymphocytic leukemia (CLL) exemplifies an aggressive malignancy that develops from an indolent neoplasm. To decipher the genetics underlying this transformation, we computationally deconvoluted admixtures of CLL and RS cells from 52 patients with RS, evaluating paired CLL-RS whole-exome sequencing data. We discovered RS-specific somatic driver mutations (including IRF2BP2, SRSF1, B2M, DNMT3A and CCND3), recurrent copy-number alterations beyond del(9p21)(CDKN2A/B), whole-genome duplication and chromothripsis, which were confirmed in 45 independent RS cases and in an external set of RS whole genomes. Through unsupervised clustering, clonally related RS was largely distinct from diffuse large B cell lymphoma. We distinguished pathways that were dysregulated in RS versus CLL, and detected clonal evolution of transformation at single-cell resolution, identifying intermediate cell states. Our study defines distinct molecular subtypes of RS and highlights cell-free DNA analysis as a potential tool for early diagnosis and monitoring.
Référence
Nat Med. 2023 01 9;:
