Abstract
Chromosome 18 is frequently rearranged in carcinomas. We explored the distribution
of breakpoints affecting chromosome 18 by mapping 56 breakpoints in 26 carcinoma cell
lines by fluorescence in situ hybridization (FISH) using bacterial artificial chromosomes
(BACs) and band paints. The distribution of breaks among 18 intervals of chromosome
18 was significantly nonrandom. The interval spanning the centromere contained the
greatest number of breaks and had the highest average copy number of any interval.
There was a high density of breaks close to the centromere as well as actually within
the centromere. A cluster of breaks encompassing SMAD4 was associated with the minimum average copy number, consistent with SMAD4 being a tumor suppressor gene. There may be another cluster of breaks around 18q12.
We offer two interpretations of the concentration of breaks near the centromere. It
may reflect selection for an oncogene near the centromere, or there may be an underlying
bias of breakage toward the centromere. We show that the latter is predicted by a
simple model that invokes random breakage following anchorage of some random point
on the chromosome, or selection of breaks proximal to one of several tumor suppressor
genes.
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Article info
Publication history
Accepted:
September 22,
2005
Received in revised form:
September 20,
2005
Received:
August 8,
2005
Identification
Copyright
© 2006 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
