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[Cancer Research 61, 818-822, February 1, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Evidence That Genetic Instability Occurs at an Early Stage of Colorectal Tumorigenesis1

Ie-Ming Shih, Wei Zhou, Steven N. Goodman, Christoph Lengauer, Kenneth W. Kinzler and Bert Vogelstein2

Howard Hughes Medical Institute [B. V.], Johns Hopkins Oncology Center [I-M. S., W. Z., S. N. G., C. L., K. W. K., B. V.], and Department of Pathology [I-M. S.], Johns Hopkins Medical Institutions, Baltimore, Maryland 21231

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.




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