CHARACTERIZATION OF A HIGH COPY NUMBER AMPLIFICATION AT 6Q24 IN PANCREATIC-CANCER IDENTIFIES C-MYB AS A CANDIDATE ONCOGENE

In a recent study designed to identify chromosomal aberrations in panc reatic cancer tissues using comparative genomic hybridization, a high copy number amplification on 6q was detected. To identify the most lik ely candidate oncogene, the extension of the amplification in pancreat ic cancer tissues and cell lines was determined by Southern blot analy sis. Exon trapping was performed with DNA from a yeast artificial chro mosome 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 hut also in the majority of the examine d pancreatic cancer tissues and cell lines, suggesting that amplificat ion is only one of the mechanisms leading to overexpression. In contra st, the novel gene, which was called human eRF3b (eukaryotic release f actor 3b), seems to be only coamplified with c-myb. Genetic alteration s of c-myb were mainly found in advanced tumors, indicating a possible correlation to tumor progression and aggressive tumor phenotypes.