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

Valind, Anders LU ; Wessman, Sandra; Pal, Niklas; Karlsson, Jenny LU ; Jonson, Tord LU ; Sandstedt, Bengt and Gisselsson, David LU (2018) In Pediatric Blood and Cancer 65(11).
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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
convergent evolution, Denys–Drash syndrome, whole exome sequencing, Wilms tumor, WT1
in
Pediatric Blood and Cancer
volume
65
issue
11
publisher
John Wiley and Sons Inc.
external identifiers
  • scopus:85050620053
ISSN
1545-5009
DOI
10.1002/pbc.27301
language
English
LU publication?
yes
id
6fa3764d-7ddb-4cf3-98aa-e2d3fa6870cc
date added to LUP
2018-10-01 10:42:04
date last changed
2019-01-06 14:06:35
@article{6fa3764d-7ddb-4cf3-98aa-e2d3fa6870cc,
  abstract     = {<p>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.</p>},
  articleno    = {e27301},
  author       = {Valind, Anders and Wessman, Sandra and Pal, Niklas and Karlsson, Jenny and Jonson, Tord and Sandstedt, Bengt and Gisselsson, David},
  issn         = {1545-5009},
  keyword      = {convergent evolution,Denys–Drash syndrome,whole exome sequencing,Wilms tumor,WT1},
  language     = {eng},
  month        = {11},
  number       = {11},
  publisher    = {John Wiley and Sons Inc.},
  series       = {Pediatric Blood and Cancer},
  title        = {Convergent evolution of 11p allelic loss in multifocal Wilms tumors arising in WT1 mutation carriers},
  url          = {http://dx.doi.org/10.1002/pbc.27301},
  volume       = {65},
  year         = {2018},
}