Analysis of chromosome breakpoints in neuroblastoma at sub‐kilobase resolution using fine‐tiling oligonucleotide array CGH

• DOI: 10.1002/gcc.20243
• Publication Date: 2005-08-03T01:26:07Z
• Authors: Rebecca R. Selzer; Todd A. Richmond; Nathan J. Pofahl; Roland D. Green; Peggy S. Eis; Prakash Nair; Arthur R. Brothman; Raymond L. Stallings
• Keywords: Breakpoint; Comparative genomic hybridization; Copy number analysis; Tiling array; Amplicon

Abstract Understanding the genes and genetic pathways targeted by recurrent chromosomal imbalances in malignancy, along with molecular mechanisms that generate imbalances, are important problems cancer biology. In this report, we demonstrate oligonucleotide array CGH (oaCGH) analysis can routinely map imbalance breakpoints at exon‐level resolution, including single copy number genomic alterations. Different tiling‐path designs were used study: a whole‐genome 6‐kb median probe spacing fine‐tiling arrays for selected regions either 50‐ or 140‐bp spacing. both formats, probes of isothermal design tiled through genic inter‐genic regions. Whole‐genome oaCGH two neuroblastoma cell lines three primary tumors led to identification 58 generated 45 large‐scale partial (>2 Mb). An unexpectedly high proportion (34%) these breakpoint intervals mapped containing segmental duplications. addition, 88 smaller‐sized (<2 Mb) detected, majority which segmentally duplicated may reflect constitutional polymorphisms. The 12 abnormalities exhibited lines, MYCN amplicon boundaries, loss 3p, 11q, gain 17q, could be ranging from 50 bp 10 kb size using high‐density microarrays. Fine‐tiling provides an unprecedented level allowing detailed mapping unbalanced abnormalities. Supplementary material article found on Genes, Chromosomes, Cancer website http://www.interscience.wiley.com/jpages/1045‐2257/suppmat/index.html . © 2005 Wiley‐Liss, Inc.