From Favorable Histology to Relapse: The Clonal Evolution of a Wilms Tumor

Jason Saliba, Natasha Belsky, Ami Patel, Kristen Thomas, William L. Carroll*, Joanna Pierro

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalPediatric and Developmental Pathology
DOIs
StateAccepted/In press - Jan 1 2019

Keywords

  • Wilms
  • blastemal histology
  • clonal evolution
  • drug resistance
  • pediatric
  • relapse

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine

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