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Background: Little is known about the genetic mechanisms of anaplastic thyroid cancer (ATC). ATC is the most virulent of all human malignancies, and it is believed to result from transformation of differentiated thyroid cancers. Purpose: To identify a set of genes involved in the development of ATC, we investigated gene expression profiles of 11 cell lines derived from ATC with a cDNA microarray representing 25,344 genes. Material & Method: RNA was extracted from 11 anaplastic thyroid cancer cell lines (ACL). For control, 10 normal thyroid tissues were collected with informed consent and RNA was extracted. Then total RNA was amplified with T7 RNA polymerase based amplification method, which amplified mRNA selectively. Amplified RNA was labeled using Cy3 for normal and Cy5 for ACL with amino allyl method. With original house-made cDNA array that contains 26 K genes and ESTs, we performed competitive hybridization. Scanned signal was normalized and then analyze the differently expressed genes between ACL and normal thyroid gland by random permutation test. Semi-quantitative RT-PCR (SQ-PCR) experiments carried out for some genes that had shown altered expression on the microarray analysis. In addition, one novel gene, OEATC-1 was identified that had oncogenic function in ATC carcinogenesis. Functional analysis of OEATC-1 was performed. Results and Discussion: Microarray analysis revealed 88 altered expressed genes in ACL. 56 genes were under-expressed and 32 genes were over-expressed. SQ-PCR verified frequent over-expression of Destrin, HSPA8, Stathmin, LDH-A, ATP5A1, PSMB6, B23, HDP-1 and LDH-B, and frequent under-expression of thyroglobulin, PBP and c-FES/FPS genes among the cell lines and also among ten primary ATC. Based on microarray results, novel genes OEATC-1 was identified. OEATC-1 was significantly over-expressed in ACL and ATC and less expressed in normal thyroid gland and other normal human tissues. Gene silencing of OEATC-1 using siRNA caused cell growth suppression, so it was suggested oncogenic function of OEATC-1 in anaplastic thyroid cancer. Conclusion: This is the first report of comprehensive gene expression profiling of anaplastic thyroid cancer. The extensive list of genes identified provides valuable information toward understanding of development of ATC, and provides a source of possible biomarkers for diagnosis and/or molecular targets for development of novel drugs to treat anaplastic thyroid cancer.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]