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Mechanisms Underlying Losses of Heterozygosity in Human Colorectal Cancers
Sam Thiagalingam, Steve Laken, James K. V. Willson, Sanford D. Markowitz, Kenneth W. Kinzler, Bert Vogelstein and Christoph Lengauer
Proceedings of the National Academy of Sciences of the United States of America
Vol. 98, No. 5 (Feb. 27, 2001), pp. 2698-2702
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3055119
Page Count: 5
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Losses of heterozygosity are the most common molecular genetic alteration observed in human cancers. However, there have been few systematic studies to understand the mechanism(s) responsible for losses of heterozygosity in such tumors. Here we report a detailed investigation of the five chromosomes lost most frequently in human colorectal cancers. A total of 10,216 determinations were made with 88 microsatellite markers, revealing 245 chromosomal loss events. The mechanisms of loss were remarkably chromosome-specific. Some chromosomes displayed complete loss such as that predicted to result from mitotic nondisjunction. However, more than half of the losses were associated with losses of only part of a chromosome rather than a whole chromosome. Surprisingly, these losses were due largely to structural alterations rather than to mitotic recombination, break-induced replication, or gene conversion, suggesting novel mechanisms for the generation of much of the aneuploidy in this common tumor type.
Proceedings of the National Academy of Sciences of the United States of America © 2001 National Academy of Sciences