Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy.
Nat Commun
; 7: 11111, 2016 Apr 05.
Article
en En
| MEDLINE
| ID: mdl-27045317
ABSTRACT
How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ADN de Neoplasias
/
Neoplasias Esofágicas
/
Adenocarcinoma
/
Terapia Neoadyuvante
/
Evolución Clonal
/
Proteínas de Neoplasias
/
Recurrencia Local de Neoplasia
/
Antineoplásicos
Idioma:
En
Año:
2016
Tipo del documento:
Article