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(American Journal of Pathology. 2003;163:2165-2172.)
© 2003 American Society for Investigative Pathology

Short Communication

A Tetraspanin-Family Protein, T-Cell Acute Lymphoblastic Leukemia-Associated Antigen 1, Is Induced by the Ewing’s Sarcoma-Wilms’ Tumor 1 Fusion Protein of Desmoplastic Small Round-Cell Tumor

Emi Ito^*, Reiko Honma^*, Jun-ichi Imai^*, Sakura Azuma, Takayuki Kanno, Shigeo Mori, Osamu Yoshie^¶, Jun Nishio^||, Hiroshi Iwasaki^||, Koichi Yoshida^**, Jin Gohda, Jun-ichiro Inoue, Shinya Watanabe^* and Kentaro Semba

From the Division of Cancer Genomics,^* the Division of Cellular and Molecular Biology, and the Division of Pathology, ^¶ Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo; Japan Biological Informatics Consortium, Hacchobori, Tokyo; the Department of Microbiology,^¶ Kinki University School of Medicine, Osaka-Sayama, Osaka; the Department of Pathology,|| School of Medicine, Fukuoka University, Fukuoka; and the Department of Biology,^** School of Medicine, Sapporo Medical University, Chuo-ku, Sapporo, Japan

Recurrent chromosomal translocations in neoplasms often generate hybrid genes that play critical roles in tumorigenesis. Desmoplastic small round-cell tumor (DSRCT) is an aggressive malignancy associated with the chromosomal translocation t(11;22)(p13;q12). This translocation generates a chimeric transcription factor, EWS-WT1, which consists of the transcriptional activation domain of the Ewing’s sarcoma (EWS) protein and the DNA binding domain of the Wilms’ tumor 1 (WT1) protein. One of the splice variants, EWS-WT1(-KTS) lacks three amino acid residues (Lys-Thr-Ser) in the DNA binding domain and transforms NIH3T3 cells. Therefore, it is likely that aberrant gene expression caused by EWS-WT1(-KTS) is involved in the malignant phenotype of DSRCT. Microarray analysis of 9600 human genes revealed that a gene encoding a tetraspanin-family protein, T-cell acute lymphoblastic leukemia-associated antigen 1 (TALLA-1), was induced in EWS-WT1(-KTS)-expressing cell clones. This induction was EWS-WT1(-KTS)-specific, and more importantly, TALLA-1 protein was expressed in the three independent cases of DSRCT. Tetraspanin-family genes encode transmembrane proteins that regulate various cell processes such as cell adhesion, migration and metastasis. Our findings provide a novel insight into the malignant phenotype of DSRCT, suggesting that TALLA-1 is a useful marker for diagnosis and a potential target for the therapy of DSRCT.

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