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Gastrointestinal stromal tumors with KIT mutations exhibit a remarkably homogeneous gene expression profile

Allander, S V; Nupponen, N N; Ringnér, Markus LU ; Hostetter, G; Maher, G W; Goldberger, N; Chen, Y; Carpten, J; Elkahloun, A G and Meltzer, P S (2001) In Cancer Research 61(24). p.8624-8628
Abstract
Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract, are believed to arise from the interstitial cells of Cajal. GISTs are characterized by mutations in the proto-oncogene KIT that lead to constitutive activation of its tyrosine kinase activity. The tyrosine kinase inhibitor STI571, active against the BCR-ABL fusion protein in chronic myeloid leukemia, was recently shown to be highly effective in GISTs. We used 13,826-element cDNA microarrays to define the expression patterns of 13 KIT mutation-positive GISTs and compared them with the expression profiles of a group of spindle cell tumors from locations outside the gastrointestinal tract. Our results showed a remarkably distinct and uniform... (More)
Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract, are believed to arise from the interstitial cells of Cajal. GISTs are characterized by mutations in the proto-oncogene KIT that lead to constitutive activation of its tyrosine kinase activity. The tyrosine kinase inhibitor STI571, active against the BCR-ABL fusion protein in chronic myeloid leukemia, was recently shown to be highly effective in GISTs. We used 13,826-element cDNA microarrays to define the expression patterns of 13 KIT mutation-positive GISTs and compared them with the expression profiles of a group of spindle cell tumors from locations outside the gastrointestinal tract. Our results showed a remarkably distinct and uniform expression profile for all of the GISTs. In particular, hierarchical clustering of a subset of 113 cDNAs placed all of the GIST samples into one branch, with a Pearson correlation >0.91. This homogeneity suggests that the molecular pathogenesis of a GIST results from expansion of a clone that has acquired an activating mutation in KIT without the extreme genetic instability found in the common epithelial cancers. The results provide insight into the histogenesis of GIST and the clinical behavior of this therapeutically responsive tumor. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Research
volume
61
issue
24
pages
8624 - 8628
publisher
American Association for Cancer Research Inc.
external identifiers
  • pmid:11751374
  • scopus:0035893766
ISSN
1538-7445
language
English
LU publication?
no
id
ec2a526d-9c33-46d8-9e6b-64b7190a9ad6 (old id 1120093)
alternative location
http://cancerres.aacrjournals.org/content/61/24/8624.long
http://cancerres.aacrjournals.org/cgi/content/abstract/61/24/8624
date added to LUP
2008-06-03 14:57:56
date last changed
2018-10-03 11:11:50
@article{ec2a526d-9c33-46d8-9e6b-64b7190a9ad6,
  abstract     = {Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract, are believed to arise from the interstitial cells of Cajal. GISTs are characterized by mutations in the proto-oncogene KIT that lead to constitutive activation of its tyrosine kinase activity. The tyrosine kinase inhibitor STI571, active against the BCR-ABL fusion protein in chronic myeloid leukemia, was recently shown to be highly effective in GISTs. We used 13,826-element cDNA microarrays to define the expression patterns of 13 KIT mutation-positive GISTs and compared them with the expression profiles of a group of spindle cell tumors from locations outside the gastrointestinal tract. Our results showed a remarkably distinct and uniform expression profile for all of the GISTs. In particular, hierarchical clustering of a subset of 113 cDNAs placed all of the GIST samples into one branch, with a Pearson correlation >0.91. This homogeneity suggests that the molecular pathogenesis of a GIST results from expansion of a clone that has acquired an activating mutation in KIT without the extreme genetic instability found in the common epithelial cancers. The results provide insight into the histogenesis of GIST and the clinical behavior of this therapeutically responsive tumor.},
  author       = {Allander, S V and Nupponen, N N and Ringnér, Markus and Hostetter, G and Maher, G W and Goldberger, N and Chen, Y and Carpten, J and Elkahloun, A G and Meltzer, P S},
  issn         = {1538-7445},
  language     = {eng},
  number       = {24},
  pages        = {8624--8628},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {Gastrointestinal stromal tumors with KIT mutations exhibit a remarkably homogeneous gene expression profile},
  volume       = {61},
  year         = {2001},
}