Progression of ductal carcinoma in situ to invasive breast cancer: comparative genomic sequencing.
Virchows Arch
; 474(2): 247-251, 2019 Feb.
Article
en En
| MEDLINE
| ID: mdl-30284611
Several models have been described as potential mechanisms for the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC). The aim of our study was to increase our understanding of DCIS progression by using massive parallel sequencing of synchronous DCIS and IBC. We included patients with synchronous DCIS and IBC (n = 4). Initially, IBC and normal tissue were subjected to whole exome sequencing. Subsequently, targeted sequencing was performed to validate those tumor-specific variants identified by whole exome sequencing. Finally, we analyzed whether those specific variants of the invasive component were also present in the DCIS component. There was a high genomic concordance between synchronous DCIS and IBC (52 out of 92 mutations were present in both components). However, the remaining mutations (40 out of 92) were restricted to the invasive component. The proportion of tumor cells with these mutations was higher in the invasive component compared to the DCIS component in a subset of patients. Our findings support the theory that the progression from DCIS to IBC could be driven by the selection of subclones with specific genetic aberrations. This knowledge improves our understanding of DCIS progression, which may lead to the identification of potential markers of progression and novel therapeutic targets in order to develop a more personalized treatment of patients with DCIS.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma Ductal de Mama
/
Carcinoma Intraductal no Infiltrante
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Virchows Arch
Asunto de la revista:
BIOLOGIA MOLECULAR
/
PATOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Alemania