RT journal article
T1 Pathogenic Variants Associated with Epigenetic Control and the NOTCH Pathway Are Frequent in Classic Hodgkin Lymphoma
A1 Santisteban Espejo, Antonio Leopoldo
A1 Bernal Florindo, Irene
A1 Montero Pavón, Pedro
A1 Pérez Requena, José
A1 Atienza Cuevas, Lidia
A1 Fernández Valle, María del Carmen
A1 Villalba Fernández, Ana
A1 García Rojo, Marcial
A2 Anatomía PatológicaBiología Celular, Histología, Historia de la Ciencia, Medicina Legal y Forense y Toxicología
A2 Cirugía
A2 Medicina
K1 classic Hodgkin lymphoma
K1 clonal evolution
K1 next-generation sequencing
K1 epigenetics
K1 personalized therapies
AB Classic Hodgkin lymphoma (cHL) constitutes a B-cell neoplasm derived from germinal center lymphocytes. Despite high cure rates (80–90%) obtained with the current multiagent protocols, a significant proportion of cHL patients experience recurrences, characterized by a lower sensitivity to second-line treatments. The genomic background of chemorefractory cHL is still poorly understood, limiting personalized treatment strategies based on molecular features. In this study, using a targeted next-generation sequencing (NGS) panel specifically designed for cHL research, we compared chemosensitive and chemorefractory diagnostic tissue samples of cHL patients. Furthermore, we longitudinally examined paired diagnosis–relapsesamples of chemorefractory cHL in order to define patterns of dynamic evolution and clonal selection. Pathogenic variants in NOTCH1 and NOTCH2 genes frequently arise in cHL. Mutations in genes associated with epigenetic regulation (CREBBP and EP300) are particularly frequent in relapsed/refractory cHL. The appearance of novel clones characterized by mutations previously not identified at diagnosis is a common feature in cHL cases showing chemoresistance to frontline treatments. Our results expand current molecular and pathogenic knowledge of cHL and support the performance of molecular studies in cHL prior to the initiation of first-line therapies.
PB MDPI
SN 1422-0067
YR 2024
FD 2024
LK http://hdl.handle.net/10498/32431
UL http://hdl.handle.net/10498/32431
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 12-nov-2026