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Characterization of a High Copy Number Amplification at 6q24 in Pancreatic Cancer Identifies c-myb as a Candidate Oncogene¹

Department of Internal Medicine I, University of Ulm, 89081 Ulm, Germany [C. W., F. M-P., G. A., T. M. G.]; German Cancer Research Center, 69120 Heidelberg, Germany [S. S-T., P. L.]; Department of Visceral and Transplantation Surgery, University of Berne, 3010 Berne, Switzerland [H. F., M. B.]; and Fachärztliches Labor Professor Seelig, 76133 Karlsruhe, Germany [T. F.]

In a recent study designed to identify chromosomal aberrations in pancreatic cancer tissues using comparative genomic hybridization, a high copy number amplification on 6q was detected. To identify the most likely candidate oncogene, the extension of the amplification in pancreatic cancer tissues and cell lines was determined by Southern blot analysis. Exon trapping was performed with DNA from a yeast artificial chromosome clone containing the complete minimally amplified region. Only fragments from two genes, namely, the c-myb oncogene and a novel gene, were shown to be amplified. The c-myb proto-oncogene was amplified in 10% of the pancreatic carcinoma tissues and in the pancreatic cancer cell line PC2. Interestingly, the c-myb oncogene was overexpressed not only in the amplified samples but also in the majority of the examined pancreatic cancer tissues and cell lines, suggesting that amplification is only one of the mechanisms leading to overexpression. In contrast, the novel gene, which was called human eRF3b (eukaryotic release factor 3b), seems to be only coamplified with c-myb. Genetic alterations of c-myb were mainly found in advanced tumors, indicating a possible correlation to tumor progression and aggressive tumor phenotypes.

¹ This work was supported by Grant 01 GB9401 from the ‘Bundesministerium für Bildung und Forschung-Förderschwerpunkt Klinisch-Biomedizinische Forschung.’

² To whom requests for reprints should be addressed. Phone: (49) 731-5024311; Fax: (49) 731-5024302.

Received 4/18/97. Accepted 6/16/97.

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