Organ-specific molecular classification of primary lung, colon, and ovarian adenocarcinomas using gene expression profiles

被引:163
作者
Giordano, TJ
Shedden, KA
Schwartz, DR
Kuick, R
Taylor, JMG
Lee, N
Misek, DE
Greenson, JK
Kardia, SLR
Beer, DG
Rennert, G
Cho, KR
Gruber, SB
Fearon, ER
Hanash, S
机构
[1] Univ Michigan, Hlth Syst, Dept Pathol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA
[6] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA
[7] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA
[8] Clalit Htlth Serv, Natl Canc Control Ctr, Haifa, Israel
[9] Univ Haifa, IL-31999 Haifa, Israel
[10] Technion Univ, Haifa, Israel
关键词
D O I
10.1016/S0002-9440(10)62509-6
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Molecular classification of tumors based on their gene expression profiles promises to significantly refine diagnosis and management of cancer patients. The establishment of organ-specific gene expression patterns represents a crucial first step in the clinical application of the molecular approach. Here, we report on the gene expression profiles of 154 primary adenocarcinomas of the lung, colon, and ovary. Using high-density oligonucleotide arrays with 7129 gene probe sets, comprehensive gene expression profiles of 57 lung, 51 colon, and 46 ovary adenocarcinomas were generated and subjected to principle component analysis and to a cross-validated prediction analysis using nearest neighbor classification. These statistical analyses resulted in the classification of 152 of 154 of the adenocarcinomas in an organ-specific manner and identified genes expressed in a putative tissue-specific manner for each tumor type. Furthermore, two tumors were identified, one in the colon group and another in the ovarian group, that did not conform to their respective organ-specific cohorts. Investigation of these outlier tumors by immunohistochemical profiling revealed the ovarian tumor was consistent with a metastatic adenocarcinoma of colonic origin and the colonic tumor was a pleomorphic mesenchymal. tumor, probably a leiomyosarcoma, rather than an epithelial tumor. our results demonstrate the ability of gene expression profiles to classify tumors and suggest that determination of organ-specific gene expression profiles will play a significant role in a wide variety of clinical settings, including molecular diagnosis and classification.
引用
收藏
页码:1231 / 1238
页数:8
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