Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents.
Nat Commun
; 7: 10767, 2016 Feb 24.
Article
en En
| MEDLINE
| ID: mdl-26908133
ABSTRACT
The cytidine analogues azacytidine and 5-aza-2'-deoxycytidine (decitabine) are commonly used to treat myelodysplastic syndromes, with or without a myeloproliferative component. It remains unclear whether the response to these hypomethylating agents results from a cytotoxic or an epigenetic effect. In this study, we address this question in chronic myelomonocytic leukaemia. We describe a comprehensive analysis of the mutational landscape of these tumours, combining whole-exome and whole-genome sequencing. We identify an average of 14±5 somatic mutations in coding sequences of sorted monocyte DNA and the signatures of three mutational processes. Serial sequencing demonstrates that the response to hypomethylating agents is associated with changes in DNA methylation and gene expression, without any decrease in the mutation allele burden, nor prevention of new genetic alteration occurence. Our findings indicate that cytosine analogues restore a balanced haematopoiesis without decreasing the size of the mutated clone, arguing for a predominantly epigenetic effect.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Azacitidina
/
Leucemia Mielomonocítica Crónica
/
Regulación Neoplásica de la Expresión Génica
/
Supervivencia Celular
/
Metilación de ADN
/
Epigénesis Genética
/
Mutación
/
Antimetabolitos Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Francia