Convergent evolution of 11p allelic loss in multifocal Wilms tumors arising in WT1 mutation carriers

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Abstract

Wilms tumors in patients with constitutional WT1 mutations are examples of Knudson's tumor suppressor paradigm, with somatic inactivation of the second allele occurring through 11p loss of heterozygosity. The time point of this second hit has remained unknown. We analyzed seven Wilms tumors from two patients with constitutional WT1 mutations by whole exome sequencing and genomic array. All tumors exhibited wild type WT1 loss through uniparental isodisomy. Each tumor had a unique genomic breakpoint in 11p, typically accompanied by a private activating mutation of CTNNB1. Hence, convergent evolution rather than field carcinogenesis underlies multifocal tumors in WT1 mutation carriers.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Karolinska University Hospital
  • Karolinska Institute
  • Skåne University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik
  • Cancer och onkologi

Nyckelord

Originalspråkengelska
Artikelnummere27301
TidskriftPediatric Blood and Cancer
Volym65
Utgivningsnummer11
StatusPublished - 2018 nov 1
PublikationskategoriForskning
Peer review utfördJa