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Clin Cancer Res. 2013 Apr 15;19(8):1960-71. doi: 10.1158/1078-0432.CCR-12-3260. Epub 2013 Feb 26.

Copy number aberrations of genes regulating normal thymus development in thymic epithelial tumors.

Author information

1
Medical Oncology Branch; Genetics Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.

Abstract

PURPOSES:

To determine whether the deregulation of genes relevant for normal thymus development can contribute to the biology of thymic epithelial tumors (TET).

EXPERIMENTAL DESIGN:

Using array comparative genomic hybridization, we evaluated the copy number aberrations of genes regulating thymus development. The expression of genes most commonly involved in copy number aberrations was evaluated by immunohistochemistry and correlated with patients' outcome. Correlation between FOXC1 copy number loss and gene expression was determined in a confirmation cohort. Cell lines were used to test the role of FOXC1 in tumors.

RESULTS:

Among 31 thymus development-related genes, PBX1 copy number gain and FOXC1 copy number loss were presented in 43.0% and 39.5% of the tumors, respectively. Immunohistochemistry on a series of 132 TETs, including those evaluated by comparative genomic hybridization, revealed a correlation between protein expression and copy number status only for FOXC1 but not for PBX1. Patients with FOXC1-negative tumors had a shorter time to progression and a trend for a shorter disease-related survival. The correlation between FOXC1 copy number loss and mRNA expression was confirmed in a separate cohort of 27 TETs. Ectopic FOXC1 expression attenuated anchorage-independent cell growth and cell migration in vitro.

CONCLUSION:

Our data support a tumor suppressor role of FOXC1 in TETs.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00965627.

PMID:
23444221
PMCID:
PMC3630263
DOI:
10.1158/1078-0432.CCR-12-3260
[Indexed for MEDLINE]
Free PMC Article
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