1. ¹Divisions of Basic Science and Human Biology, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington, Seattle, WA, USA
2. ²Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
3. ³Department of Animal and Food Sciences, University of Delaware, Newark, DE, USA
4. ⁴DNA Array Facility, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

Correspondence: Dr PE Neiman, Divisions of Basic Science and Human Biology, Fred Hutchinson Cancer Research Center and Department of Medicine, 1100 Fairview Ave. N., C2-023, Seattle, WA 98109-1024, USA. E-mail: pneiman@fhcrc.org

Received 15 September 2005; Revised 1 February 2006; Accepted 29 March 2006; Published online 1 May 2006.

Abstract

Retroviral vector-mediated overexpression of c-myc in embryonic bursal precursors induces multi-staged tumorigenesis beginning with preneoplastic-transformed follicles (TF) and progressing to clonal metastatic B-cell lymphomas. Using a 13K chicken cDNA microarray, specifically enriched for chicken immune system expressed sequence tagged (ESTs), we carried out array-based comparative genomic hybridization (array-CGH) and detected significant DNA copy number change at many loci on most or all chromosomes in both early TF and end-stage lymphomas. Formation of long palindromes, through breakage–fusion–bridge cycles, is thought to play an early role in gene amplification. Employing genome-wide analysis of palindrome formation (GAPF), we detected extensive palindrome formation in early TF and end-stage lymphomas. The population of loci showing amplification by array-CGH was enriched for palindromes detected by GAPF providing strong evidence for genetic instability early in Myc-induced tumorigenesis and further support for the role of palindromes in gene amplification. Comparing gene copy number change and RNA expression changes profiled on the same cDNA array, we detected very little consistent contribution of gene copy number change to RNA expression changes. Palindromic loci in TF and tumors, however, were expressed, many at high levels, suggesting an abundance of RNA species with long double-stranded segments generated during tumorigenesis.