From Favorable Histology to Relapse: The Clonal Evolution of a Wilms Tumor
| Autor: | William L. Carroll, Joanna Pierro, Kristen Thomas, Natasha Belsky, Ami Patel, Jason Saliba |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Drug resistance Wilms Tumor Somatic evolution in cancer Pathology and Forensic Medicine Clonal Evolution Biological pathway Necrosis 03 medical and health sciences 0302 clinical medicine Recurrence medicine Humans business.industry Wilms' tumor General Medicine medicine.disease Kidney Neoplasms Neoadjuvant Therapy Protein Phosphatase 2C 030104 developmental biology Child Preschool 030220 oncology & carcinogenesis Favorable histology Pediatrics Perinatology and Child Health Cancer research Female business |
| Zdroj: | Pediatric and Developmental Pathology. 23:167-171 |
| ISSN: | 1615-5742 1093-5266 |
| DOI: | 10.1177/1093526619875919 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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