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Squamous Cell Carcinoma Related Oncogene/DCUN1D1 Is Highly Conserved and Activated by Amplification in Squamous Cell Carcinomas

¹ Laboratory of Epithelial Cancer Biology, ² Head and Neck Service, ³ Thoracic Surgery Service, and ⁴ Department of Pathology, Memorial Sloan-Kettering Cancer Center; ⁵ Laboratory of Cancer Biology, Rockefeller University, New York, New York; and ⁶ Children's Cancer Center, Baylor College of Medicine, Houston, Texas

Requests for reprints: Bhuvanesh Singh, Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Phone: 212-639-2024; Fax: 212-717-3302; E-mail: singhb{at}mskcc.org.

Chromosomal amplification at 3q is common to multiple human cancers, but has a specific predilection for squamous cell carcinomas (SCC) of mucosal origin. We identified and characterized a novel oncogene, SCC-related oncogene (SCCRO), which is amplified along the 3q26.3 region in human SCC. Amplification and overexpression of SCCRO in these tumors correlate with poor clinical outcome. The importance of SCCRO amplification in malignant transformation is established by the apoptotic response to short hairpin RNA against SCCRO, exclusively in cancer cell lines carrying SCCRO amplification. The oncogenic potential of SCCRO is underscored by its ability to transform fibroblasts (NIH-3T3 cells) in vitro and in vivo. We show that SCCRO regulates Gli1—a key regulator of the hedgehog (HH) pathway. Collectively, these data suggest that SCCRO is a novel component of the HH signaling pathway involved in the malignant transformation of squamous cell lineage. (Cancer Res 2006; 66(19): 9437-44)

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