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Clear cell sarcoma of the kidney demonstrates an embryonic signature indicative of a primitive nephrogenic origin.

Karlsson, Jenny LU ; Holmquist Mengelbier, Linda LU ; Ciornei, Cristina LU ; Naranjo, Arlene; O'Sullivan, Maureen J and Gisselsson Nord, David LU (2014) In Genes, Chromosomes and Cancer 53(5). p.381-391
Abstract
Clear cell sarcoma of the kidney (CCSK) is a tumor affecting children with a median age of 3 years at diagnosis. The cell of origin of CCSK is unknown and data on the molecular changes giving rise to CCSK is scarce. This has hindered the identification of positive diagnostic markers and development of molecularly targeted treatment protocols for CCSK. We have characterized a panel of CCSK to gain information regarding its molecular profile and possible origin. High-resolution genomic analysis with single nucleotide polymorphism array of 37 tumors did not reveal any clues to the mechanisms behind tumor development as remarkably few genetic imbalances were found. Gene expression analysis revealed a highly characteristic gene signature,... (More)
Clear cell sarcoma of the kidney (CCSK) is a tumor affecting children with a median age of 3 years at diagnosis. The cell of origin of CCSK is unknown and data on the molecular changes giving rise to CCSK is scarce. This has hindered the identification of positive diagnostic markers and development of molecularly targeted treatment protocols for CCSK. We have characterized a panel of CCSK to gain information regarding its molecular profile and possible origin. High-resolution genomic analysis with single nucleotide polymorphism array of 37 tumors did not reveal any clues to the mechanisms behind tumor development as remarkably few genetic imbalances were found. Gene expression analysis revealed a highly characteristic gene signature, enriched for pathways involved in embryonic development, including kidney formation. The presence of markers for two different developmental lineages in the embryonic kidney was therefore investigated in the tumor cells. FOXD1 which identifies cells giving rise to stromal elements, and CITED1, a marker for cells primed for nephrogenic epithelial differentiation, were both highly expressed in CCSK. In addition, the early embryonic marker OSR1 was expressed at higher levels in CCSK than in Wilms tumor, normal fetal kidney or adult kidney. As this marker discriminates the intermediate mesoderm from other mesodermal structures, our study could suggest that CCSK arises from a mesodermal cell type that retains the capacity to initiate differentiation towards both nephrons and stroma, but remains locked in a primitive state. © 2014 Wiley Periodicals, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
53
issue
5
pages
381 - 391
publisher
John Wiley & Sons
external identifiers
  • pmid:24488803
  • wos:000332695000002
  • scopus:84895926355
ISSN
1045-2257
DOI
10.1002/gcc.22149
language
English
LU publication?
yes
id
5f8cc9c9-1cab-48ae-bb44-18bd6a7524d2 (old id 4335870)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24488803?dopt=Abstract
date added to LUP
2014-03-07 20:24:01
date last changed
2017-10-22 03:15:47
@article{5f8cc9c9-1cab-48ae-bb44-18bd6a7524d2,
  abstract     = {Clear cell sarcoma of the kidney (CCSK) is a tumor affecting children with a median age of 3 years at diagnosis. The cell of origin of CCSK is unknown and data on the molecular changes giving rise to CCSK is scarce. This has hindered the identification of positive diagnostic markers and development of molecularly targeted treatment protocols for CCSK. We have characterized a panel of CCSK to gain information regarding its molecular profile and possible origin. High-resolution genomic analysis with single nucleotide polymorphism array of 37 tumors did not reveal any clues to the mechanisms behind tumor development as remarkably few genetic imbalances were found. Gene expression analysis revealed a highly characteristic gene signature, enriched for pathways involved in embryonic development, including kidney formation. The presence of markers for two different developmental lineages in the embryonic kidney was therefore investigated in the tumor cells. FOXD1 which identifies cells giving rise to stromal elements, and CITED1, a marker for cells primed for nephrogenic epithelial differentiation, were both highly expressed in CCSK. In addition, the early embryonic marker OSR1 was expressed at higher levels in CCSK than in Wilms tumor, normal fetal kidney or adult kidney. As this marker discriminates the intermediate mesoderm from other mesodermal structures, our study could suggest that CCSK arises from a mesodermal cell type that retains the capacity to initiate differentiation towards both nephrons and stroma, but remains locked in a primitive state. © 2014 Wiley Periodicals, Inc.},
  author       = {Karlsson, Jenny and Holmquist Mengelbier, Linda and Ciornei, Cristina and Naranjo, Arlene and O'Sullivan, Maureen J and Gisselsson Nord, David},
  issn         = {1045-2257},
  language     = {eng},
  number       = {5},
  pages        = {381--391},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Clear cell sarcoma of the kidney demonstrates an embryonic signature indicative of a primitive nephrogenic origin.},
  url          = {http://dx.doi.org/10.1002/gcc.22149},
  volume       = {53},
  year         = {2014},
}