Evidence that genetic instability occurs at an early stage of colorectal tumorigenesis

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 re...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2001-02, Vol.61 (3), p.818-822
Main Authors: SHIH, Ie-Ming, WEI ZHOU, GOODMAN, Steven N, LENGAUER, Christoph, KINZLER, Kenneth W, VOGELSTEIN, Bert
Format: Article
Language:English
Subjects:
Adenoma - genetics
Adenoma - pathology
Allelic Imbalance
APC gene
Biological and medical sciences
chromosome 1
chromosome 10
chromosome 15
chromosome 5
chromosome 8
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
DNA Primers
DNA, Neoplasm - genetics
Gastroenterology. Liver. Pancreas. Abdomen
Genetic Markers - genetics
Humans
Medical sciences
Polymerase Chain Reaction - methods
Polymorphism, Single Nucleotide
Probability
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445