From Favorable Histology to Relapse: The Clonal Evolution of a Wilms Tumor.
Pediatr Dev Pathol
; 23(2): 167-171, 2020.
Article
em En
| MEDLINE
| ID: mdl-31526128
ABSTRACT
Favorable histology (FH) Wilms tumor (WT) is one of the most curable of all human cancers, yet a small minority of patients fail treatment. The underlying biological pathways that lead to therapy resistance are unknown. We report a case of initially unresectable, FH WT which revealed limited necrosis and persistent blastemal predominant histology following neoadjuvant chemotherapy. Despite intensification of therapy and whole abdominal radiation, the patient relapsed and succumbed to her disease. In an effort to discover candidate drivers of drug resistance, whole exome sequencing and copy number analysis were performed on samples from all 3 tumor specimens. Sequencing results revealed outgrowth of clones with a dramatically different genetic landscape including dominant mutations that could explain therapy evasion, some of which have not been previously reported in WT. Our results implicate PPM1D, previously shown to be associated with drug resistance in other tumors, as the major driver of treatment failure.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tumor de Wilms
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Proteína Fosfatase 2C
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Neoplasias Renais
Limite:
Child, preschool
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Female
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Humans
Idioma:
En
Revista:
Pediatr Dev Pathol
Assunto da revista:
PATOLOGIA
/
PEDIATRIA
Ano de publicação:
2020
Tipo de documento:
Article