Copy Number Aberrations of Genes Regulating Normal Thymus Development in Thymic Epithelial Tumors

被引:32
作者
Petrini, Iacopo [1 ]
Wang, Yisong [1 ]
Zucali, Paolo A. [3 ]
Lee, Hye Seung [1 ,4 ]
Trung Pham [1 ]
Voeller, Donna [1 ]
Meltzer, Paul S. [2 ]
Giaccone, Giuseppe [1 ]
机构
[1] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA
[2] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA
[3] IRCCS, Humanitas Canc Ctr, Dept Med Oncol, Milan, Italy
[4] Seoul Natl Univ, Bundang Hosp, Dept Pathol, Songnam, Gyeonggi, South Korea
关键词
BREAST-CANCER; DNA METHYLATION; LUNG ADENOCARCINOMA; DRUG-SENSITIVITY; CELL-GROWTH; ORGANOGENESIS; EXPRESSION; CARCINOMA; SURVIVAL; FOXC1;
D O I
10.1158/1078-0432.CCR-12-3260
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. Clin Cancer Res; 19(8); 1960-71. (C) 2013 AACR.
引用
收藏
页码:1960 / 1971
页数:12
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