Abstract
Chromosomal instability is believed to be a common feature of most human tumors, but the stage at which such instability originates has not been defined. At the molecular level, chromosomal instability is characterized by allelic imbalance (AI), representing losses or gains of defined chromosomal regions. We have assessed AI in early colorectal tumors using newly developed methods for assessing AI in complex cell populations. A total of 32 adenomas of average size (2 mm; range, 1–3 mm) were studied. AI of chromosome 5q markers occurred in 55% of tumors analyzed, consistent with a gatekeeping role of the adenomatous polyposis coli tumor suppressor gene located at chromosomal position 5q21. AI was also detected in each of the other four chromosomes tested. The fractions of adenomas with AI of chromosomes 1p, 8p, 15q, and 18q were 10, 19, 28, and 28%, respectively. Over 90% of the tumors exhibited AI of at least one chromosome, and 67% had allelic imbalance of a chromosome other than 5q. These findings demonstrate that AI is a common event, even in very small tumors, and suggest that chromosomal instability occurs very early during colorectal neoplasia.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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4 W. Zhou, G. Galizia, S. Goodman, K. Romans, E. Lieto, K. W. Kinzler, B. Vogelstein, M. Choti, and E. Montgomery, unpublished observations.
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↵1 This work was supported by the Clayton Fund, the V Foundation, and NIH Grants CA43460, CA 57345, and CA62924.
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↵2 To whom requests for reprints should be addressed, at Johns Hopkins Oncology Center, 1650 Orleans Street, Baltimore, MD 21231. E-mail: vogelbe{at}welch.jhu.edu
- Received October 12, 2000.
- Accepted December 13, 2000.
- ©2001 American Association for Cancer Research.
Volume 61, Issue 3
