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Histological specificity of alterations and expression of KIT and KITLG in non-small cell lung carcinoma.

Salomonsson, Annette LU ; Jönsson, Mats LU ; Isaksson, Sofi LU ; Karlsson, Anna ; Jönsson, Per LU ; Gaber, Alexander LU ; Bendahl, Pär-Ola LU ; Johansson, Leif LU ; Brunnström, Hans LU orcid and Jirström, Karin LU orcid , et al. (2013) In Genes, Chromosomes and Cancer 52(11). p.1088-1096
Abstract
Characterization of molecules within important oncogenetic pathways may have future implications for development of therapies and biomarkers in lung cancer. One such target is the tyrosine kinase receptor KIT (c-KIT). We evaluated alterations and expression of KIT and its ligand, KITLG (also known as SCF), in 72 clinical lung tumor specimens of different histologies. Gene copy number, mRNA expression levels, and protein expression were assayed using array-based comparative genomic hybridization, real-time quantitative reverse transcription PCR and immunohistochemistry, respectively. For validation, we investigated copy number alterations and mRNA expression in external microarray data sets of 1,600 and 555 primary lung tumors,... (More)
Characterization of molecules within important oncogenetic pathways may have future implications for development of therapies and biomarkers in lung cancer. One such target is the tyrosine kinase receptor KIT (c-KIT). We evaluated alterations and expression of KIT and its ligand, KITLG (also known as SCF), in 72 clinical lung tumor specimens of different histologies. Gene copy number, mRNA expression levels, and protein expression were assayed using array-based comparative genomic hybridization, real-time quantitative reverse transcription PCR and immunohistochemistry, respectively. For validation, we investigated copy number alterations and mRNA expression in external microarray data sets of 1,600 and 555 primary lung tumors, respectively. Positivity for KIT staining was most common in large cell neuroendocrine carcinoma (LCNEC) which also showed the highest KIT mRNA expression levels whereas expression was lowest in squamous cell carcinoma (SqCC). KIT mRNA expression levels were higher in KIT immunopositive samples, but expression was not affected by KIT copy numbers. Copy number gains of KIT were significantly more frequent in SqCC compared with adenocarcinoma in our own series and in the 1,600-sample data set. Immunopositivity for both KIT and KITLG in the same tumor was rare except in LCNEC. Our results highlight an increased KIT mRNA expression and frequent KIT immunopositivity in LCNEC but point out a poor correlation between KIT copy numbers and expression in SqCC, perhaps reflecting the existence of a protective mechanism against KIT alterations in this subgroup. © 2013 Wiley Periodicals, Inc. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
52
issue
11
pages
1088 - 1096
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000325106700009
  • pmid:24019021
  • scopus:84884704288
  • pmid:24019021
ISSN
1045-2257
DOI
10.1002/gcc.22103
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000), Oncology, MV (013035000), Department of Clinical Sciences, Lund (013230000)
id
30f5fb4f-57a1-4f2f-abb4-0b4e86134e31 (old id 4066141)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24019021?dopt=Abstract
date added to LUP
2016-04-01 11:09:34
date last changed
2024-01-22 07:35:13
@article{30f5fb4f-57a1-4f2f-abb4-0b4e86134e31,
  abstract     = {{Characterization of molecules within important oncogenetic pathways may have future implications for development of therapies and biomarkers in lung cancer. One such target is the tyrosine kinase receptor KIT (c-KIT). We evaluated alterations and expression of KIT and its ligand, KITLG (also known as SCF), in 72 clinical lung tumor specimens of different histologies. Gene copy number, mRNA expression levels, and protein expression were assayed using array-based comparative genomic hybridization, real-time quantitative reverse transcription PCR and immunohistochemistry, respectively. For validation, we investigated copy number alterations and mRNA expression in external microarray data sets of 1,600 and 555 primary lung tumors, respectively. Positivity for KIT staining was most common in large cell neuroendocrine carcinoma (LCNEC) which also showed the highest KIT mRNA expression levels whereas expression was lowest in squamous cell carcinoma (SqCC). KIT mRNA expression levels were higher in KIT immunopositive samples, but expression was not affected by KIT copy numbers. Copy number gains of KIT were significantly more frequent in SqCC compared with adenocarcinoma in our own series and in the 1,600-sample data set. Immunopositivity for both KIT and KITLG in the same tumor was rare except in LCNEC. Our results highlight an increased KIT mRNA expression and frequent KIT immunopositivity in LCNEC but point out a poor correlation between KIT copy numbers and expression in SqCC, perhaps reflecting the existence of a protective mechanism against KIT alterations in this subgroup. © 2013 Wiley Periodicals, Inc.}},
  author       = {{Salomonsson, Annette and Jönsson, Mats and Isaksson, Sofi and Karlsson, Anna and Jönsson, Per and Gaber, Alexander and Bendahl, Pär-Ola and Johansson, Leif and Brunnström, Hans and Jirström, Karin and Borg, Åke and Staaf, Johan and Planck, Maria}},
  issn         = {{1045-2257}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1088--1096}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Genes, Chromosomes and Cancer}},
  title        = {{Histological specificity of alterations and expression of KIT and KITLG in non-small cell lung carcinoma.}},
  url          = {{http://dx.doi.org/10.1002/gcc.22103}},
  doi          = {{10.1002/gcc.22103}},
  volume       = {{52}},
  year         = {{2013}},
}