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Research Articles: Therapeutics, Targets, and Development

C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer

¹ Vaccinex, Inc.; ² The James P. Wilmot Cancer Center; and Departments of ³ Medicine and ⁴ Pathology, University of Rochester School of Medicine and Dentistry, Rochester, New York

Requests for reprints: Elizabeth E. Evans, Vaccinex, Inc., Rochester, 1875 Mt. Hope Avenue, Rochester, NY 14620. Phone: 585-271-2700; Fax: 585-271-2766. E-mail: eevans{at}vaccinex.com

Abstract

Identification of shared tumor-specific targets is useful in developing broadly applicable therapies. In a study designed to identify genes up-regulated in breast cancer, a cDNA clone corresponding to a novel gene C35 (C17orf37) was selected by representational difference analysis of tumor and normal human mammary cell lines. Abundant expression of C35 transcript in tumors was confirmed by Northern blot and real-time PCR. The C35 gene is located on chromosome 17q12, 505 nucleotides from the 3' end of the ERBB2 oncogene, the antigenic target for trastuzumab (Herceptin^TM) therapy. The chromosomal arrangement of the genes encoding C35 and ERBB2 is tail to tail. An open reading frame encodes a 12-kDa protein of unknown function. Immunohistochemical analysis detected robust and frequent expression of C35 protein, including 32% of grade 1 and 66% of grades 2 and 3 infiltrating ductal carcinomas of the breast (in contrast to 20% overexpressing HER-2/neu), 38% of infiltrating lobular carcinoma (typically HER-2/neu negative), as well as tumors arising in other tissues. C35 was not detected in 38 different normal human tissues, except Leydig cells in the testes and trace levels in a small percentage of normal breast tissue samples. The distinct and favorable expression profile of C35 spanning early through late stages of disease, including high frequency of overexpression in various breast carcinoma, abundant expression in distant metastases, and either absence or low level expression in normal human tissues, warrants further investigation of the relevance of C35 as a biomarker and/or a target for development of broadly applicable cancer-specific therapies. [Mol Cancer Ther 2006;5(11):2919–30]

Grant support: Vaccinex, NIH Small Business Innovative Research grant 1R43/2R44 CA80440, and U.S. Army grant DAMD17-99-1-9419.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ R. Gupta et al. Prediction of N-glycosylation sites in human proteins. 2004, in preparation.

⁶ In preparation.

Received 7/ 6/06; revised 8/23/06; accepted 9/25/06.